Phosphonates containing sulfur and selenium. Synthesis of vinylphosphonates bearing α-sulfenyl, α-selenenyl, α-sulfinyl and α-seleninyl moieties and studies on nucleophilic addition

Article abstract of DOI:10.1016/j.tet.2004.10.026

The selenenylation of racemic and optically active α-phosphoryl sulfoxides is a key step leading efficiently to α-phosphorylvinyl sulfoxides or α-phosphorylvinyl selenides depending on the reaction conditions. Oxidation of α-phosphorylvinyl selenides and subsequent thermolysis of selenoxides afford alkynylphosphonates. Studies of the stereochemical course of nucleophilic addition to α-phosphoryl sulfoxides show high facial stereoselectivity of the reaction, however, epimerisation at the α-carbon atom leads to mixtures of diastereomers. Graphical Abstract

Full text of DOI:10.1016/j.tet.2004.10.026

Tetrahedron 60 (2004) 12217–12229
Phosphonates containing sulfur and selenium. Synthesis of
vinylphosphonates bearing a-sulfenyl, a-selenenyl, a-sulfinyl and
a-seleninyl moieties and studies on nucleophilic addition
*
Wanda H. Midura and Jerzy A. Krysiak
Department of Heteroorganic Chemistry, Center of Molecular and Macromolecular Studies, Polish Academy of Sciences,
´ ´
90-363 Łodz, Sienkiewicza 112, Poland
Received 28 July 2004; revised 13 September 2004; accepted 7 October 2004
Abstract—The selenenylation of racemic and optically active a-phosphoryl sulfoxides is a key step leading efficiently to a-phosphorylvinyl
sulfoxides or a-phosphorylvinyl selenides depending on the reaction conditions. Oxidation of a-phosphorylvinyl selenides and subsequent
thermolysis of selenoxides afford alkynylphosphonates. Studies of the stereochemical course of nucleophilic addition to a-phosphoryl
sulfoxides show high facial stereoselectivity of the reaction, however, epimerisation at the a-carbon atom leads to mixtures of diastereomers.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
2. Results and discussion
Functionalized vinylphosphonates have attracted much
interest in synthetic chemistry and their synthetic appli-
cations have been widely investigated in the last two
decades.1,2 In recent years, special attention has been
devoted to a-heterosubstituted vinylphosphonates as useful
intermediates for the synthesis of natural products.3–5
2.1. Synthesis
One of the best methods to introduce a C–C double bond is
the selenenylation and subsequent oxidative selenoxide
elimination. In a classical procedure PhSeX (XZCl, Br,
SePh) is used for introduction of the selenenyl moiety. An
alternative selenenylation method, developed by Liotta8 for
selenenylation of ketones, involves addition of elemental
selenium to enolate anions. This method seems to be a
cheaper and easier procedure. In order to find a general
methodology for the synthesis of vinylphosphonates, we
decided to define the scope and limitations of the selenium
addition procedure.
Recently, we have designed6 and investigated a new type of
vinylphosphonate with a sulfinyl substituent as a stereo-
control element. These vinylphosphonates were found to
easily undergo Michael reaction, Diels–Alder cycloaddition
and cyclopropanation by reaction with sulfur ylides and
diazoalkanes. Various types of asymmetric reaction using
these a-phosphorylvinyl sulfoxides have been investigated6b,7
and found to proceed in some cases with considerably high
stereoselectivity, which has been attributed to differen-
tiation of the p-faces induced by the sulfinyl group. In this
paper, we wish to describe the full account of our studies on
the synthesis of our target compounds and investigations
into nucleophilic addition.
We have found that the a-lithioalkanephosphonates,
obtained from the phosphonates 1 and n-butyllithium in
THF solution at K78 8C, react with elemental selenium,
which is simply added to the reaction mixture as a powder.9
Dissolution of selenium was observed to take place at
K30 8C and above affording the corresponding lithium
selenoates. The latter, without isolation, were easily
converted into the corresponding methyl selenides 2 by
treatment with methyl iodide (Scheme 1).
Phosphonates 2a,b possessing b-hydrogen atoms were
converted into vinylphosphonates 3a,b by oxidation to the
corresponding selenoxides followed by their spontaneous
elimination under the reaction conditions. The utility of this
Keywords: Selenenylation; a-Phosphoryl-vinyl sulfoxides; a-Phosphoryl-
vinyl selenoxides; Nucleophilic addition.
* Corresponding author. Tel.: C48 42 681 5832; fax: C48 42 684 7126;
e-mail: whmidura@bilbo.cbmm.lodz.pl
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.10.026

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W. H. Midura, J. A. Krysiak / Tetrahedron 60 (2004) 12217–12229
Scheme 1.
Scheme 2.
approach for vinylphosphonate synthesis was demonstrated
by the synthesis of diethyl a-methylthiovinylphosphonate
4a (Scheme 2).
On the other hand, selective oxidation of the vinyl sulfide 4a
by means of H2O2 in pyridine solution leads to the
corresponding vinyl sulfoxide 5a, however, this reaction
affords the desired compound only in racemic form.
Because our interest is focused on the utilization of chiral
sulfoxides in asymmetric synthesis we elaborated a new
procedure for the synthesis of the optically active sulfoxides
5 starting from the optically active sulfoxides 7,11 which are
mixtures of two diastereomers (SCSS)/(RCSS) in a 2:1 ratio
(Scheme 4). Thus, the lithium salt of the a-phosphoryl
sulfoxide 7b was found to undergo the reaction with
elemental selenium and after methylation and oxygenation
afforded the vinyl sulfoxide 5b in above 50% yield.
Unfortunately, it turned out that the addition of selenium
does not occur cleanly as in the case of simple phosphonates
1 and in the reaction mixture, in addition to the desired
a-phosphorylselenothioketal S-oxide 8, different side pro-
ducts were found. One of them was identified as the
corresponding selenothioketal 9—a sulfoxide reduction
product. The latter in the next step undergoes oxidation
leading to racemic 5b (path b). Because oxidative
elimination of selenenic acid must be performed on a
crude reaction mixture (to avoid sulfenic acid elimination),
this reduction–oxidation process decreases the optical purity
of the sulfoxide 5b [a]DC123 (c, 1.2 acetone) (Scheme 4).
The mechanism of this reduction is not clear.
The synthesis of a-phosphorylvinyl sulfides 4 in Scheme 2
is complementary to the earlier syntheses of these
compounds, that is, the addition of methanesulfenyl
chloride to diethyl vinylphosphonate followed by hydro-
chloride elimination10a and the Peterson reaction of a-silyl
a-phosphoryl sulfides.10b a-Phosphoryl vinyl sulfides 4
easily undergo oxidation and they can be transformed into
the vinyl sulfones 6 using H2O2 in acetone solution
(Scheme 2). An alternative method for the introduction of
the methylene moiety at the carbon atom possessing
strongly electron-withdrawing groups is the Mannich
reaction. The reaction of a-phosphoryl sulfone with
paraformaldehyde in the presence of a catalytic amount of
piperidine and acetic acid also afforded the vinyl sulfone 6
in moderate to high yield (42–73%) (Scheme 3).
The efficient and highly stereoselective synthesis of the
enantiopure sulfoxide 5b was accomplished using
Scheme 3.

W. H. Midura, J. A. Krysiak / Tetrahedron 60 (2004) 12217–12229
12219
Scheme 4.
phenylselenenyl bromide as the selenenylating agent. Thus,
the a-carbanion of a-diethoxyphosphorylethyl p-tolyl sulf-
oxide 7b, formed on treatment with n-butyllithium in THF
at K78 8C, reacted with PhSeBr and after 3 min the reaction
mixture was quenched with cold aqueous solution of
NaHCO3. Extraction with ethyl ether afforded the PhSe-
substituted sulfoxide 10, of unknown diastereomeric ratio,
since only one broad signal in the 31P NMR spectrum was
visible. To complete the synthesis of a-phosphorylvinyl
sulfoxide 5b, oxidation of the selenide moiety was
performed using H2O2 in CH2Cl2 solution at 0 8C which
caused benzeneselenenic acid elimination and formation of
the desired product (Scheme 5).
42 Hz for E and 23.3 and 23.1 Hz for Z isomers,
respectively.
The PhSe-substituted phosphoryl sulfoxides 10, which upon
oxidation undergo transformation to a-phosphorylvinyl
sulfoxides 5, can also afford a,b-unsaturated selenides 11
(Scheme 6). When 10 was heated in a benzene solution,
elimination of sulfenic acid took place resulting in the
formation of a-phosphorylvinyl selenides 11 in high yields
(72–88%). Elimination of p-toluenesulfenic acid from
10b,c,d occurs quite easily and the full conversion requires
heating at 80 8C during the course of a few hours (4–5 h).
The conversion of 10a to 11a, where the loss of
methanesulfenic acid takes place, requires a longer time
(ca. 10 h) at the same temperature.
This methodology was extended to the synthesis of
b-substituted a-phosphorylvinyl sulfoxides 5c and 5d.
They were obtained from a-phosphorylpropyl p-tolyl
sulfoxide 7c and a-phosphorylhexyl p-tolyl sulfoxide 7d
(optically pure at the sulfur atom) according to the
procedure described above (Scheme 5).
From a preparative point of view, it is worth noting that
sulfoxide elimination from 10c,d was found to take place at
room temperature when they were subjected to chromato-
graphy on a silica gel column. In contrast to stereoselective
selenoxide elimination of 10, the sulfoxide elimination
leads to a 1:1 mixture of E and Z isomers, which were easily
separated by column chromatography.
It is interesting to underline that the oxidative selenoxide
elimination affords vinyl sulfoxides 5c,d as mixtures of
E and Z isomers in about 10:1 ratio. After purification by
column chromatography both isomers were separated,
however, the minor Z-isomer was contaminated with a
small amount of the starting material. The configuration of
the a,b-unsaturated sulfoxides 5c,d was determined12 based
on the 3JP–H coupling constants values which were 41.4 and
Oxidation of vinyl selenides 11 yields selenoxides 12 in
very high yields. It was found that a-phosphorylvinyl
selenoxides E and Z-12 differ in stability. Whereas the
isomer E can be stored for a few days, the isomer Z easily
loses its oxygen (1 day, rt), reverting to starting selenide and
Scheme 5.

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W. H. Midura, J. A. Krysiak / Tetrahedron 60 (2004) 12217–12229
Scheme 6.
cannot be purified by chromatography. The better stability
of the isomer E-12, where the substituent at the a-carbon
atom is on the same side of a double bond as the bulky
phosphoryl group, can be attributed to hydrogen bonding
between the selenoxide oxygen and the vinyl hydrogen.13
sulfoxide would be destroyed in further transformations
(after the Horner reaction or desulfurization), much more
interesting from the synthetic point of view is the chirality
on the b-carbon atom. In order to establish the stereo-
chemical course of nucleophilic addition to vinylphos-
phonates with b-substituent, some reactions with different
nucleophiles were performed using a-phosphorylvinyl
sulfoxides 5c, 5d and 5e and a-phosphorylvinyl selenides
and selenoxides 11c and 12c as Michael acceptors.
Owing to the presence of the selenoxide moiety, the
a-phosphoryl vinyl selenoxides 12 were found to undergo
further syn-elimination. Hence, the thermolysis of 12b, and
E-12c and E-12d performed in refluxing (benzene solution
affords a-phosphorylalkynes 13 as the only products. In this
way a new synthetic approach to this class of compounds
was elaborated.14
The addition of Me2NH to E and Z selenides 11c afforded
the adducts 14 as mixtures of diastereomers in a 10:1 and
2:1 ratio, respectively (Scheme 8). Typical oxidation of 14
with H2O2 in CH2Cl2 gives two major products, whose ratio
depends on the reaction conditions. At room temperature,
the only product was the E-vinyl selenoxide 12c. Probably,
this temperature favours oxidation of the amine moiety to
the corresponding amine oxide, which after elimination,
gives rise to a rather stable vinyl selenoxide. With
decreasing temperature the selenoxide elimination takes
place forming enamine, which, however, undergoes
hydrolysis under the reaction and work-up conditions
affording b-ketophosphonate 15 as the major product. For
this reason no information about the steric course of the
reaction can be drawn from these experiments.
2.2. Nucleophilic addition
a-Phosphorylvinyl sulfoxides 5 as well as a-phosphoryl-
vinyl selenoxides 12 having two electron-withdrawing
groups are effective acceptors in conjugate addition of
nucleophiles. Taking into account an easy way of
elimination of selenenic and sulfenic acid, the sulfoxide 5
and selenoxide 12 can be considered as equivalents of
a-phosphoryl alkynes in nucleophilic addition. On the other
hand, as we mentioned before, nucleophilic addition to
chiral sulfoxides 5 should occur under stereochemical
control by the sulfinyl group.
Since nucleophilic addition to the selenide 11c gave no
answer concerning the steric course of the addition, the next
experiments were performed using the vinyl selenoxide 12c
as starting material. Addition of the malonate anion to
a-phosphorylvinyl selenoxide E-12c occurs easily, but
affords the product of isomerization i.e., the b,g-unsaturated
phosphonate 16. Probably, in this case the equilibrium
between a,b and b,g-isomers is shifted to the latter. To
exclude the possibility of this isomerization 2-nitropropane
was used in our further studies. The reaction with the
potassium salt of 2-nitropropane with E-12c afforded only
the Z-isomer of the vinylphosphonate 17 and allylic alcohol
18c as a side reaction product. The latter was undoubtedly
formed as a result of a,b to b,g-isomerization and allylic
Our first experiments of nucleophilic addition were
perfomed using the vinyl sulfoxide 5b and various
heteronucleophiles: dimethylamine, ethyl mercaptan in the
presence of Et3N and methanol in the presence of KOH. In
all cases, addition occurred easily at room temperature
affording the desired products as a mixture of diastereomers
in around 2:1 ratio. This ratio is determined by thermo-
dynamic factors which was established by equilibration
using the isolated pure diastereomers. The reaction with the
lithium salt of diethyl malonate also affords the correspond-
ing addition product as a mixture of diastereomers in the
same ratio (Scheme 7).
Since the chirality of the a-carbon atom in a-phosphoryl

W. H. Midura, J. A. Krysiak / Tetrahedron 60 (2004) 12217–12229
12221
Scheme 7.
Scheme 8.
rearrangement of the starting material 12c under the
reaction conditions (Scheme 9).
selenoxides 12. Unfortunately, the reaction of the
Z-isomer of 12 with the potassium salt of 2-nitropropane
gave a mixture of the same products and additionally
some amount of the E-isomer of starting material,
suggesting the presence of the equilibrium either between
E and Z isomers of starting vinyl selenoxides 12 or threo
and erythro Michael adducts. Taking into account the
easy selenoxide elimination (Michael addition product
was not detected), the Z/E isomerization of 12 through
allylic selenoxide probably occurs much faster than
nucleophilic addition of a bulky nitropropane and only
the more stable trans isomer undergoes Michael addition
selectively affording the product Z-17.
The structure of the vinylphosphonate 17 was confirmed
by NMR studies using nuclear Overhauser effect.
Irradiation of the vinyl proton caused 21% increase of
the methyl protons and irradiation of the methyl group of
Z-17 (dP 16.8) gave a 17% enhancement of the vinyl
proton. This indicates that these two moieties are on the
same side of the olefinic bond. The Z-geometry of the
vinylphosphonate 17 obtained as well as the fact of cis-
geometry of selenoxide elimination, imply anti-approach
during nucleophilic addition to the a-phosphorylvinyl

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W. H. Midura, J. A. Krysiak / Tetrahedron 60 (2004) 12217–12229
Those products could be formed when nucleophilic addition
to sulfoxide 5 partly occurs in anti and partly in syn-manner,
what is rather unlikely because anti-addition was suggested
in our model reaction with selenoxide 12c. Another
explanation presumes stereoselective attack of nucleophile
leading to only one diastereomer of 19 and partial
epimerization on the a-carbon atom under the reaction
conditions (Scheme 10).
Addition of the lithium salt of diethyl malonate to E-(C)-
(1-dimethoxyphosphoryl-2-phenyl)vinyl p-tolyl sulfoxide
50e affords a mixture of four diastereomers 190e dP: 21.2/
20.9/22.4/21.5 ppm in a 22:15:3:2 ratio. Oxidation of the
major pair of diastereomers (21.2/20.9) as well as the minor
one (22.4/21.5) separately in order to destroy chirality at
sulfur, gave in both cases a mixture of the sulfone 210e
(18.3/17.9), that is the diastereomers of threo and erythro
configuration. Also in this case we can presume anti
addition of the malonate nucleophile leading to diastereo-
mers A and B and then formation of diastereomers C and D
caused by epimerisation on the a-carbon atom. According to
our recent studies of asymmetric cyclopropanation of
a-phosphorylvinyl sufoxides with sulfur ylides,13 the
major factor controlling the stereoselectivity of this reaction
is the conformation of the sulfoxide, where sulfinyl and
phosphoryl groups adopt an anti orientation, the former
being syncoplanar with the carbon–carbon double bond.
Nucleophilic addition of the sulfur ylide occurs exclusively
from the less-hindered diastereotopic face occupied by the
electron lone pair at sulfur. Although we do not have any
configurational assignment of addition products 190e, it
seems likely, that major diastereomer 190e (dP: 21.2 ppm)
has configuration A, formed by the same facial nucleophilic
attack of the lithium salt of diethyl malonate (Schemes 11
and 12).
Scheme 9.
Nucleophilic addition to b-substituted a-phosphorylvinyl
sulfoxides is more complex since the reaction should create
two centres of chirality under stereochemical control of the
sulfinyl group. Having in hand three chiral sulfoxide
substrates (5c,d,50e15) we decided to extend the studies on
the nucleophilic addition and its stereoselectivity. In the
reaction of (E)-(S)-(1-diethoxyphosphoryl-2-methyl)vinyl
p-tolyl sulfoxide 5c with the lithium salt of diethyl
malonate, generated by LiH in THF solution, the desired
adduct 19c was formed exclusively as a 5:3 mixture of two
(from four) possible diastereomers. The product 19 upon
storage at room temperature slowly undergoes sulfoxide
elimination yielding the vinylphosphonate 20. However, in
this case the 31P NMR spectra indicated the presence of both
E and Z isomers of 20 formed. Taking into account
configurational requirement for syn-elimination of sulfenic
acid, the presence of two isomers of 20 suggests that they
were formed from 19 of threo and erythro configuration.
Nucleophilic addition of the sodium salt of 2-nitropropane
to E-(C)-(1-dimethoxyphosphoryl-2-phenyl)vinyl p-tolyl
Scheme 10.

W. H. Midura, J. A. Krysiak / Tetrahedron 60 (2004) 12217–12229
12223
Scheme 11.
Scheme 12.
sulfoxide 50e was performed in a similar way to selenoxides.
It was found that elimination of sulfenic acid from the
primary adduct is so fast, that it can not be detected in 31P
NMR spectra. Also in this case only one vinylphosphonate
was obtained (dP 17.5), because instantaneous sulfenic acid
elimination from the adduct makes epimerization
impossible.
g-Hydroxy- phosphonate 18d, obtained in this way,
exhibited optical rotation [a]DC1.5 (c, 0.8 acetone).
According to the H NMR spectra in the presence of (C)-
1
(R)-t-butylphenylphosphinothioic acid this value corre-
sponds only to 5% ee. Trying to improve the asymmetric
induction, we decreased the temperature to K15 8C. In this
case the reaction was complete after 3 days, but we were
able to raise the optical purity of the product 18 to 25%
[a]DC8.1 (c, 0.5 acetone). Because the typical procedure
for SPAC reaction applied to a-phosphoryl sulfoxides
requires rather vigorous conditions18 (heating at 40 8C for
12–24 h), our modification using a,b-unsaturated a-phos-
phoryl sulfoxides seems to give the possibility to obtain
optically active g-hydroxyphosphonates (Scheme 13).
2.3. Allylic alcohol synthesis
The synthesis of different types of g-hydroxy a,b-
unsaturated derivatives from sulfoxides and aldehydes was
described as a one step procedure16 (SPAC reaction, an
abbreviation from sulfoxide piperidine aldehyde conden-
sation) based on a sequence of reactions: Knoevenagel
condensation, prototropic shift and allylic sulfoxide–
sulfenate rearrangement. Usually, the SPAC reaction was
carried in CH3CN in the presence of piperidine at 0 to 60 8C.
Using chiral sulfoxides, these reactions gave rise to
asymmetric induction ranging from 10–70% ee.17 In the
case of sulfoxides 5c and 5d, the presence of a g-hydrogen
in the aliphatic chain creates the possibility of a,b to b,g
isomerization and sigmatropic rearrangement leading to
allylic alcohol 18. This reaction, confirmed already for the
analogous vinyl selenoxide 12c, also occurs in the case of
vinyl sulfoxide 5d affording g-hydroxyhexenylphosphonate
18d in excellent yield.
We have developed a general methodology to prepare
a-heterosubstituted vinylphosphonates. The crucial step of
The first experiment leading to allylic alcohol was
conducted using optically active a-phosphorylvinyl sulf-
oxide 5d by addition of Me2NH at 0 8C in CH2Cl2 solution.
Scheme 13.

12224
W. H. Midura, J. A. Krysiak / Tetrahedron 60 (2004) 12217–12229
the synthesis is selenenylation of phosphonates either by
phenylselenyl bromide, or elemental selenium, although
some limitations of the letter reagent were defined.
Applying our procedure we synthesized for the first time,
in optically active and racemic form, a,b-unsaturated
a-phosphoryl sulfoxides, important reagents in asymmetric
synthesis. Our studies on the nucleophilic addition to
a-phosphorylvinyl sulfoxides, due to epimerization of
addition products, allowed us to present only considerations
of the most probable stereochemistry of the process.
(neat) 1240, 1024; 31P NMR (81 MHz, CDCl3) d
28.18 ppm; 1H NMR (200 MHz) d: 0.84–0.93 (m, 3H,
CH3CH2); 1.14–1.43 (m,10H: 6H of t, CH3CH2OPC4H of
m, (CH2)2CH3)); 1.45–2.01 (m, 4H, –(CH2)2–); 2.12 (s, 1H,
SeCH3); 2.57 (dt, H, C–H, JP–HZ15 Hz, JH–HZ10 Hz);
4.16 (dq, 4H, CH3CH2OP, JP–HZ8.8 Hz, JH–HZ7.1 Hz);
13C NMR (50 MHz, CDCl3) d 4.5; 13.9; 16.3 (d, JZ
6.0 Hz); 22.3; 27.5 (d, JZ12.0 Hz); 28.3; 31.1; 33.9; 65.5
(d, JZ13.8 Hz); 77Se NMR (57 MHz, CDCl3) d 485 ppm;
HRMS (70 eV) C11H25O3PSe requires 316.0700 Found:
316.0697.
3. Experimental
3.1. General
3.2.3. Diethyl (a-methylselenenyl-a-phenyl)methylphos-
phonate 2c. A pale yellow oil. Yield: 5.35 g (83%); nDZ
1.5380; 31P NMR (81 MHz, CDCl3) d 23.98 ppm; 1H NMR
(200 MHz, CDCl3) d: 1.23 ppm (2xt, 6H, CH3CH2O, JZ
1H, 13C, 77Se and 31P NMR spectra were recorded on a
Bruker MSL 300 and Bruker AC 200 Spectrometer, using
deuterochloroform as solvent. Mass spectra were recorded
on Finnigan MAT95. IR spectra were recorded on Ati
Mattson FTIR Spectrometer. The optical rotations were
measured on a Perkin–Elmer 241 MC photopolarimeter in
acetone solution. The microanalyses were performed on
Elemental Analyzer EA 1108.
7.1 Hz); 2.05 (s, 3H, SeCH3); 4.02 (d, 1H, CHPh, JP–HZ
17.4 Hz); 3.23–4.23 (m, 4H, CH3CH2OP); 7.27–7.47
(m, 5H, Ar–H); 13C NMR (50 MHz, CDCl3) d 6.2 (d, JZ
3.3 Hz); 16.2 (t, JZ6.9 Hz); 36.9 (d, JC–PZ149 Hz); 63.1
(d, JZ16.5 Hz); 127.5; 128.5; 129.2; 135.7; 77Se NMR
(CDCl3, 57 MHz) d 606 ppm; HRMS (70 eV) C12H19
O3PSe requires 322.0237 Found 322.02369.
3.2.4. Diethyl (a-methylselenenyl-a-methylsulfenyl)-
methylphosphonate 2d. A slightly yellow oil. Yield:
4.26 g (73%); nDZ1.4742; 31P NMR (81 MHz, CDCl3) d
21.08 ppm; 1H NMR (200 MHz) d: 1.34 (t, 6H, CH3CH2OP,
JH–HZ7.1 Hz); 2.20 (d, 3H, SCH3, JP–HZ0.7 Hz); 2.27 (d,
3H, SeCH3, JP–HZ1.7 Hz); 3.74 (d, 1H, CH, JP–HZ15 Hz);
TLC was carried out on silica gel plates (Merck F254) and
silica gel 60 (70-230 ASTM) was used for chromatography.
THF was freshly distilled over potassium/benzophenone.
3.2. General procedure for preparation of a-phosphoryl
selenides 2
4.19 (dq, 4H, OCH2CH3, JP–HZ8.8 Hz, JH–HZ7.1 Hz); 13
C
NMR (50 MHz, CDCl3); d 5.6; 16.0 (d, JZ11.8 Hz); 16.4
(d, JP–CZ5.6 Hz); 36.2 (d, JP–CZ154.7 Hz); 63.5 (d, JP–C
6.9 Hz); HRMS (70 eV) C7H17O3PSSe requires 291.9801.
To a stirred solution of phosphonate 1 (20 mmol) in 100 mL
of dry THF, a solution of n-BuLi (10 mL, 2.2 M in hexane,
22 mmol) was added at K78 8C. After 10 min, selenium
powder (20 mmol) was added and the reaction mixture was
warmed to appropriate temperature (K30 8C—2a;
K20 8C—2b,c; K40 8C—2d) and kept at this temperature
until the selenium disappeared. Then, the reaction mixture
was cooled to K78 8C and methyl iodide (20 mmol) was
added. The reaction solution was warmed up and treated
with 30 mL of aqueous NH4Cl. The organic layer was
separated and collected with the 50 mL of chloroform
extract of the water layer. The combined organic solution
was dried over MgSO4 and the solvent was evaporated to
give the yellow oil. Purification was performed using
column chromatography on silica gel (eluent: benzene–
acetone 10:1).
Z
Found 291.9797.
3.2.5. Diethyl (a-methylselenenyl-a-methylsulfenyl)-
ethylphosphonate 2e. A slightly yellow oil. Yield: 4.41 g
(72%); nDZ1.4215; 31P NMR (81 MHz, CDCl3): d
1
23.7 ppm; H NMR (200 MHz, CDCl3): d 1.35 (2!t, 6H,
CH3CH2OP, JH–HZ7.1 Hz); 1.77 (3H, d, CH3, JP–H
Z
5.3 Hz); 2.16 (d, 3H, SeCH3, JP–HZ1.5 Hz); 2.23 (d, 3H,
SMe, JP–HZ0.2 Hz); 4.24 (dq, 4H, CH3CH2OP, JP–H
Z
8.8 Hz, JH–HZ7.1 Hz,); 13C NMR (50 MHz, CDCl3): d 5.2;
13.7 (d, JZ3.3 Hz); 16.3 (d, JZ5.9 Hz); 23.3; 43.1 (d, JZ
155 Hz); 63.6 (t, JZ7.2 Hz); 77Se NMR (57 MHz, CDCl3):
d 636 ppm; HRMS C8H19O3PSSe requires 305.9958. Found
305.9965.
3.2.1. Diethyl (a-methylselenenyl)ethylphosphonate 2a.
A pale yellow oil. Yield: 4.42 g (85%); nDZ1.4860; IR (neat)
1241, 1028;31P NMR (81 MHz, CDCl3) d 28.7 ppm;1H NMR
(200 MHz, CDCl3): d 1.3 (t, 6H, CH3CH2OP, JZ7.1 Hz);
1.54(dd, 3H, CH3CH, JP–HZ17.4 Hz, JH–HZ7.5 Hz);2.15(s,
3.3. Oxidation of a-phosphoryl selenides
To a solution of a-phosphoryl selenide (15 mmol) in 50 mL
of dry pyridine, 30% solution of hydrogen peroxide
(15 mmol) was added. The mixture was stirred vigorously
at room temperature for 2 h. Then 50 mL of diethyl ether
was added and the reaction mixture was washed with water
(5!10 mL). The organic layer was dried and solvent
evaporated affording vinylphosphonates which were
purified by column chromatography (hexane–acetone 15:1).
3H, SeCH3); 2.76 (dq, 1H, CH3CH, JP–HZ13.2 Hz, JH–H
Z
Z
7.5 Hz); 4.14 (dq, 4H, CH3CH2OP, JP–HZ8.0 Hz, JH–H
7.1 Hz); 13C NMR (50 MHz, CDCl3) d 4.5; 15.7; 16.3 (d, JP–
CZ6 Hz); 25.5 (d, JP–CZ52.2 Hz); 62.5 (d, JP–CZ6.9 Hz);
77Se NMR (57 MHz, CDCl3) d 536 ppm; HRMS (70 eV)
C7H17O3PSe requires 260.0087 Found: 260.0075.
3.3.1. Diethyl hexen-1-ylphosphonate 3b. A slightly
yellow oil. Yield: 3.17 g (96%); nDZ1.6828 (isomer E);
31P NMR (81 MHz, CDCl3) d 19.7 ppm (E)/18.1 ppm (Z)
3.2.2. Diethyl (a-methylselenenyl)hexylphosphonate 2b.
A slightly yellow oil. Yield: 5.30 g (84%); nDZ1.4732; IR

W. H. Midura, J. A. Krysiak / Tetrahedron 60 (2004) 12217–12229
12225
1
21:1; H NMR (200 MHz, CDCl3): d 0.89 (t, 3H, CH3,
a mixture of 5 drops of piperidine and 10 drops of acetic
acid and the solution was heated in reflux for 0.5 h.
a-Phosphoryl sulfone (1 mmol) was added all at once and
the solution was heated in reflux under Dean–Stark water
separator for 54 h. The solvent was removed and product
was purified by column chromatography (hexane–acetone
20:1).
JH–HZ6.8 Hz); 1.31 (t, 6H, OCH2CH3, JH–HZ7.1 Hz);
1.23–1.45 (m, 4H, CH2); 2.14–2.24 (m, 2H, CH2); 4.05 (dq,
4H, CH3CH2OP, JP–HZ8.0 Hz, JZ7.1 Hz); (for isomer Z)
5.55 (tdd, 1H, JH–HZ1.6, 7.0, 13.0 Hz, JP–HZ17.0 Hz);
6.55 (tdd, 1H, JH–HZ7.0, 11.0 Hz, JP–HZ46.3 Hz); (for the
isomer E) 5.63 (tdd, 1H, ]C–H2, JP–HZ21.2 Hz, JH–H
Z
1.5, 17.1 Hz,); 6.77 (tdd, 1H, ]CH2, JP–HZ22.0 Hz,
JH–HZ6.6, 17.1 Hz); 13C NMR (CDCl3, 50 MHz); d 13.6;
16.1 (d, JZ6.3 Hz); 21.9, 29.7, 33.6 (d, JZ21.6 Hz); 61.3
(d, JZ5.4 Hz); 116.5 (d, JZ188 Hz); 153.8 (d, JZ4.6 Hz);
HRMS (70 eV) C10H21O3P requires 220.1228. Found
220.1214.
3.5.1. Diethyl (a-methylsulfonyl)vinylphosphonate 6a.
A pale yellow oil. Yield: 0.182 g (42%)—Method B; nDZ
1.5620; IR (neat) 1250, 1019; 31P NMR (81 MHz, CDCl3): d
7.8 ppm; 1H NMR (200 MHz, CDCl3): d 1.33 (t, 6H,
CH3CH2OP, JZ7.1 Hz); 3.16 (s, 3H, SO2CH3); 4.10–4.20
(m, 4H, CH3CH2OP); 6.98 (d, 1H, JP–HZ17.3 Hz, cis
C]CH); 7.12 (d, 1H, JP–HZ39.3 Hz, trans C]CH); 13C
NMR (CDCl3, 50 MHz); 16.6 (d, JZ7.9 Hz); 18.7; 62.8;
131 (d, JZ7.1 Hz); 139 (d, JZ171 Hz). Anal. Calcd for
C7H15O5PS: C, 34.71%; H, 6.24%. Found: C, 34.83%; H,
6.32%.
3.3.2. Diethyl (a-methylsulfenyl)vinylphosphonate 4a. A
slightly yellow oil. Yield: 2.83 g (90%); nDZ1.4868; IR
(neat) 1632, 1243, 1026; 31P NMR (81 MHz) d 14.5 ppm;
1H NMR (200 MHz): d 1.34 (2!t, 6H, JZ7.1 Hz); 2.31
(s, 3H, SCH3); 4.05 (dq, 4H, JH–HZ7.1 Hz, JP–HZ8.8 Hz);
5.55 (d, 1H, JP–HZ42.9 Hz); 6.18 (d, 1H, JP–HZ21.2 Hz);
13C NMR (50 MHz, CDCl3): d 4.4 (d, JZ6.2 Hz); 15.9
(d, JZ6.9 Hz); 62.3 (d, JZ4.8 Hz); 121.5 (d, JZ7.6 Hz);
136.1 (d, JZ19.7 Hz); HRMS (70 eV) C7H15O3PS requires
210.0479. Found 210.04715.
3.5.2. a-Diethyl (1-p-tolylsulfonyl)vinylphosphonate 6b.
A pale yellow oil. Yield: 0.232 g (73%); nDZ1.5718; IR
(neat) 1590, 1261, 1024; 31P NMR (81 MHz, CDCl3): d
7.6 ppm; 1H NMR (200 MHz, CDCl3): d 1.25 (t, 6H,
CH3CH2OP, JZ7.1 Hz); 2.43 (s, 3H, Ar–CH3); 4.00–4.23
(m, 4H, CH3CH2OP); 6.94 (d, 1H, JP–HZ18.4 Hz, cis
C]CH); 7.18 (d, 1H, JP–HZ37.5 Hz, trans C]CH); 7.32
and 7.81 (4H, aromatic); 13C NMR (CDCl3, 50 MHz); d
16.0; 21.4; 63.1 (d, JZ5.3 Hz); 126.3; 127.8; 128.6; 128.9;
132.9, (d, JZ9.0 Hz); 143.2 (d, JZ106 Hz). Anal. Calcd for
C13H19O5PS: C, 49.05%; H, 6.02%. Found: C, 49.11%; H,
6.13%.
3.4. Oxidation of a-phosphorylvinyl methyl sulfide 4a to
sulfoxide 5a
a-Phosphorylvinyl methyl sulfide 4a (1 mmol) was dis-
solved in pyridine (50 mL) and 30% hydrogen peroxide
(1 mmol) was added. The mixture was stirred for 6 days at
room temperature and then Et2O (50 mL) was added. The
organic solution was washed with water (5!10 mL), dried
and evaporated. Sulfoxide 5a was purified by column
chromatography on silica gel (hexane–acetone 20:1).
3.6. Synthesis of optically active a-phosphorylvinyl
sufoxides 5
Yield: 0.266 g (85%); nDZ1.54443. A slightly yellow oil;
IR (neat) 1595, 1254, 1027, 1043; 31P NMR (81 MHz,
CDCl3): d 10.22 ppm; 1H NMR (200 MHz, CDCl3): d 1.34
(2!t, 6H, JZ7.1 Hz); 2.79 (s, 3H, SOCH3); 4.15 (4H, dq,
JP–HZ8.8 Hz, JH–HZ7.1 Hz); 6.69 (d, 1H, JH–HZ19.3 Hz,
cis C]CH); 6.77 (d, 1H, JZ40.2 Hz, trans C]CH); 13C
NMR (CDCl3, 50 MHz): d 11.1, 15.6 (d, JZ6.2 Hz); 63.9
(d, JZ89.4 Hz); 125.38 (d, JZ100.7 Hz); 133.9 (d, JZ
104 Hz); HRMS (70 eV) C7H15O4PS requires 226.0428.
Found 226.0426.
Method A. To a stirred solution of optically active
a-(diethylphosphoryl)-ethyl p-tolyl sulfoxide 7b (1.52 g,
5 mmol) in 100 mL of dry THF a 2.2 M solution of
n-butyllithium (5.5 mmol) in hexane was added dropwise at
K78 8C. After 5 min, powder of selenium (0.4 g, 5 mmol)
was added. The mixture was warmed slowly to K10 8C
when dissolution of selenium was observed. A clear dark
brown solution was treated then with methyl iodide (0.61 g,
5 mmol) and after 5 min the solution was quenched with
50 mL of aqueous solution of NH4Cl. Organic solvents were
evaporated and the remaining aqueous solution was
extracted with chloroform (2!30 mL). The CHCl3 extract
was dried over anhydrous MgSO4 and evaporated giving
mixture of products 31P NMR: 19.8 ppm (8 major product),
24.3 ppm (9–10%). The mixture was dissolved in 50 mL of
CH2Cl2 and 2 mL of H2O2/water (1:1) was added at 0 8C
and the reaction was stirred vigorously at this temperature
for 2 h. Then 30 mL of water was added. The extraction
with CH2Cl2 afforded the crude product 5b which was
purified by column chromatography (hexane–acetone 10:1).
3.5. Preparation of diethyl a-phosphorylvinyl
methylsulfone 6a
Method A (by oxidation of the sulfoxide). The diethyl
(a-methylsulfinyl)vinylphosphonate (1 mmol) was dis-
solved in acetone and two molar excess of hydrogen
peroxide was added. The reaction mixture was heated in
reflux for 2 h. On the next water (10 mL) was added and
acetone was evaporated. The water layer was extracted with
chloroform (3!15 mL). The combined organic layers were
dried by magnesium sulfate and solvents were evaporated.
The colourless oil was separated and purified by column
chromatography (hexane–acetone 20:1). Yield 0.2 g (89%).
Method B. To a stirred THF solution (100 mL) of optically
active a-phosphoryl sulfoxide 7 (10 mmol) 5 mL of 2.2 M
n-BuLi in hexane solution (11 mmol) was added at K78 8C.
After 5 min solution of phenylselenyl bromide (0.011 mol),
prepared by addition of equimolar amount of bromine to
10 mL of THF solution of diphenyldiselenide, was added all
Method B (by Mannich reaction). Paraformaldehyde
(2 mmol) was dissolved in 100 mL of benzene containing

12226
W. H. Midura, J. A. Krysiak / Tetrahedron 60 (2004) 12217–12229
at once. The reaction mixture was stirred for 2–3 min and
then poured to the cooled to 0 8C mixture of 20 mL of
diethyl ether and 20 mL of aqueous solution of sodium
carbonate. The organic layer was separated, dried over
MgSO4 and the solvent evaporated affording compound 10.
a-Phenylselenyl substituted a-phosphoryl sulfoxide 10 was
then oxidized in CH2Cl2 solution (100 mL) using 3 mL of
H2O2/water mixture in 1:1 ratio. a-Phosphorylvinyl sulf-
oxide 5 prepared in this way was purified by column
chromatography.
1H NMR (200 MHz, CDCl3): d 1.32 (td, 6H, JH–HZ7.0 Hz,
JP–HZ0.6 Hz, CH3CH2OP); 3.95–4.25 (m, 4H, CH3CH2-
OP); 5.73 (d, 1H, JP–HZ44 Hz); 6.61 (d, 1H, JP–H
Z
20.4 Hz); 7.3–7.65 (m, 5H aromatic). 13C (50 MHz,
CDCl3); d 15.6 (d, JZ7.3 Hz); 61.2 (d, JZ5.5 Hz);
118.23 (d, JZ8.1 Hz); 134.1 (d, JZ181.2 Hz); 126.2;
127.3; 130.3; 131.7. Anal. Calcd for C12H17O3PSe: C,
45.15%; H, 5.37%. Found C, 45.31%; H, 5.48%.
3.7.2. a-Diethyl (1-phenylselenenyl)propenylphos-
phonate 11c. A yellow pale oil. Yield: 0.276 g (83%);
ratio of E/Z isomers 1:1 separated by column chromato-
graphy hexane–acetone 30:1. Isomer E: IR (neat) 1610,
3.6.1. a-Diethyl (1-p-tolylsulfinyl)vinylphosphonate 5b.
A colourless oil. Yield: 2.11 g (70%); [a]DZC157 (c, 2.1,
acetone); IR (neat) 1243,1021; 31P NMR (81 MHz, CDCl3)
d 9.8 ppm; 1H NMR (200 MHz, CDCl3): d 1.18 (t, 1H, JZ
7.2 Hz); 2.39 (s, 3H, CH3Ar); 3.89–4.22 (m, 4H, CH3CH2-
OP); 6.72 (d, 1H, JP–HZ18.8 Hz, cis C]CH); 6.96 (d, 1H,
JP–HZ39.8 Hz, trans C]CH); 7.28–7.57 (4H, aromatic).
13C NMR (50 MHz, CDCl3); d 15.5 (2!d, JZ7.7 Hz);
21.1; 62.3 (d, JZ5.7 Hz); 126.0; 129.4; 132.1(d, JZ
5.5 Hz); 138.8; 142.3; 146.5 (d, JZ177.4 Hz). Anal.
Calcd for C13H19O4PS: C, 51.65%; H, 6.33%. Found C,
51.78; H, 6.52%.
1
1245, 1027; 31P NMR (81 MHz, CDCl3): d 14.6 ppm; H
NMR (200 MHz, CDCl3): d 1.25 (t, 6H, JH–HZ7.1 Hz,
CH3CH2OP); 2.12 (dd, 3H, JH–HZ7.3 Hz, JP–HZ3.2 Hz,
CH3C]); 3.8–4.2 (m, 4H, CH3CH2OP); 6.66 (dq, 1H,
JP–HZ46 Hz, JH–HZ7.3, HC]); 7.2–7.6 (m, 5H, aro-
matic); 13C NMR (50 MHz, CDCl3) 15.8 (d, JZ6.5 Hz);
18.5 (d, JZ17.0 Hz); 62.0 (d, JZ5.8 Hz); 120.5 (d, JZ
17.0 Hz); 126.4; 130.2; 130.6; 154.2 (d, JZ13.8 Hz); 77Se
NMR (57 MHz, CDCl3) d 283.6, JZ19.2 Hz. Isomer Z: 31
P
1
NMR (81 MHz, CDCl3) d 15.7 ppm; H NMR (200 MHz,
CDCl3): d 1.26 (dt, 6H, JH–HZ7.1 Hz, JP–HZ0.5 Hz,
CH3CH2O); 2.10 (dd, 3H, JP–HZ3.0 Hz, JH–HZ6.9 Hz,
CH3C]); 3.9–4.25 (m, 4H, CH3CH2OP); 7.52 (dq, 1H,
JP–HZ19.1 Hz, JH–HZ6.9 Hz, HC]); 7.2–7.5 (m, 5H,
aromatic). 13C NMR (50 MHz, CDCl3): d 16.1 (d, JZ
6.7 Hz); 18.4 (d, JZ6.4 Hz); 62.1 (d, JZ5.4 Hz); 120.5 (d,
JZ189.5 Hz); 126.4; 128.6; 130.2; 130.6; 154.2 (d, JZ
13.8 Hz). Anal. Calcd for C13H19O3PSe: C, 46.86%; H,
5.75%. Found: C, 46.93%; H, 5.91%.
3.6.2. a-Diethyl (1-p-tolylsulfinyl)-propen-1-ylphospho-
nate 5c. A colourless oil. Yield (ECZ): 2.08 g (66%).
1
Isomer Z: 31P NMR (81 MHz, CDCl3): d 12.1 ppm; H
NMR (200 MHz, CDCl3):d 1.21 (t, 3H, JZ7.2 Hz,
CH3CH2O); 1.32 (t, 3H, JZ7.2 Hz, CH3CH2O,); 2.29 (dd,
3H, JZ7.3; 2.9 Hz, CH3-Z); 2.41 (s, 3H, CH3Ar); 4.0–4.23
(m, 4H, CH3CH2O); 7.43 (dq, 1H, JH–HZ7.4 Hz, JP–H
Z
23.3 Hz); 7.25–7.68 (4H, aromatic). Isomer E: 31P NMR
(81 MHz, CDCl3): d 10.1 ppm; 1H NMR (200 MHz,
CDCl3): d 1.12; 1.16 (2!t, 6H, CH3CH2O); 2.22 (dd, 3H,
JP–HZ3.1 Hz, JH–HZ7.3 Hz); 2.35 (s, 3H, CH3Ar); 3.6–4.2
(m, 4H, CH3CH2O); 7.35 (dq, 1H, JP–HZ41.3 Hz); 7.20–
7.58 (4H, aromatic). Anal. Calcd for C14H21O4PS: C,
53.15%, H, 6.69%. Found C, 53.37%; H, 6.75%.
3.7.3. a-Diethyl (1-phenylselenenyl)hexenylphosphonate
11d. A yellow pale oil. Yield: 0.322 g (86%); ratio of E/Z
isomers 1:1. Separated isomer E: 31P NMR (81 MHz,
1
CDCl3): d 14.7 ppm; H NMR (200 MHz, CDCl3): d 0.8–
1.6 (m, 7H); 1.25 (6H, t, JH–HZ7.0 Hz, CH3CH2OP); 2.57
(tdd, 2H, JH–HZ7.8, 7.2 Hz, JP–HZ2.6 Hz, CH2C]); 4.0
3.6.3. a-Diethyl (1-p-tolylsulfinyl)-1-hexen-1-ylphos-
phonate 5d. A colourless oil. Yield (ECZ): 2.28 g (63%).
Isomer E: [a]DZC98 (c, 1.2 acetone); 31P NMR (81 MHz,
CDCl3): d 10.4 ppm; 1H NMR (200 MHz, CDCl3): d 0.93 (t,
3H, JH–HZ7.1 Hz); 1.12; 1.16 (2!t, 6H, JH–HZ7.1 Hz);
1.20–1.57 (m, 4H,); 2.37 (s, 3H, CH3Ar); 2.53 (m, 2H);
3.56–3.99 (m, 4H, CH3CH2O); 7.29 (dt, 1H, JP–HZ41.4 Hz,
JH–HZ7.9 Hz); 7.22–7.57 (4H, aromatic) 13C (50 MHz,
CDCl3): d 13.4; 15.7; 21.0; 21.9; 29.6 (d, JZ6.2 Hz); 30.3;
61.7 (d, JZ5.0 Hz); 126.1; 129.2; 134.8(d, JZ181.3 Hz);
140.5; 146.6; 150.5(d, JZ7.5 Hz).
(4H, m, CH3CH2OP); 6.58 (dt, 1H, JP–HZ46 Hz, JH–HZ
7.8 Hz, HC]); 7.25–7.56 (5H, aromatic). 13C NMR
(50 MHz, CDCl3): 13.2; 15.8 (d, JZ6.1 Hz); 21.8; 30.2;
34.4 (d, JZ22.1 Hz); 62.1 (d, JZ5.7 Hz); 117.1 (d, JZ
185 Hz); 147.2 (d, JZ5.7 Hz); 126.1; 126.9; 130.7; 131.2.
Anal. Calcd for C16H25O3PSe: C, 51.21%; H, 6.71%.
Found: C, 51.45%, H, 6.95%.
3.8. Oxidation of selenides 11 to selenoxides 12
Method A. 2 mmol of the selenide 11 was dissolved in
acetone (10 mL) and aqueous solution of sodium meta-
periodate (2 mmol) was added dropwise at 0 8C. The
reaction mixture was kept overnight in refrigerator and on
the next day 20 mL of water added and extracted with
CHCl3 (3!15 mL).
3.7. Preparation of a-phosphorylvinyl selenides 11
a-Phosphoryl a-phenylselenenyl sulfoxide 10 (1 mmol)
obtained from a-phosphoryl sulfoxide according to the
procedure described for preparation of a-phosphorylvinyl
sulfoxides was dissolved in 10 mL of benzene and heated
under reflux for 2 h. Evaporation of benzene afforded the
crude product 11.
Method B. To a solution of 2 mmol of the selenide 11 in
CH2Cl2 0.25 mL of 30% H2O2 was added and reaction
mixture was stirred vigorously for 15 min. After then 10 mL
of water was added and reaction was extracted with
(3!10 mL) CH2Cl2.
3.7.1. a-Diethyl (1-phenylselenenyl)vinylphosphonate
11b. A yellow pale oil. Yield: 0.281 g (88%); IR (neat)
1610, 1245, 1024; 31P NMR (81 MHz, CDCl3): d 14.9 ppm;
3.8.1. 1-(Diethoxyphosphoryl)vinyl phenyl selenoxide

W. H. Midura, J. A. Krysiak / Tetrahedron 60 (2004) 12217–12229
12227
12b. A slightly yellow oil. Yield: 0.67 g (w100%); IR
(neat) 1243, 1025, 843; 31P NMR (81 MHz, CDCl3) d
10.8 ppm; 1H NMR (200 MHz, CDCl3) d: 1.15 (t, 6H,
JH–HZ7.1 Hz, CH3CH2OP); 3.7–4.2 (m, 4H, CH3CH2OP);
6.77 (dd, 1H, JP–HZ18.4 Hz, JH–HZ1 Hz, cis C]CH);
7.12 (dd, 1H, JH–HZ1 Hz, JP–HZ41.1 Hz, trans C]CH);
7.4–7.82 (m, 5H, aromatic).
(81 MHz, CDCl3): d 5.4 ppm; 1H NMR (200 MHz, CDCl3):
d 0.92 (t, 3H, JZ7.1 Hz); 1.22–1.60 (m, 2H); 1.37 (dt, 6H,
JH–HZ7.0 Hz, JP–HZ0.7 Hz, CH3CH2OP); 2.35 (dt, 2H,
JH–HZ7.0 Hz, JP–HZ4.4 Hz); 4.15 (dq, 4H, JP–HZ8.6 Hz,
JH–HZ7.0 Hz, CH3CH2OP). HRMS (70 eV) C10H19O3P
requires 218.1072. Found 218.1032.
3.10. Nucleophilic addition to a-phosphorylvinyl p-tolyl
sulfoxide 5c
3.8.2. 1-(Diethylphosphoryl)propenyl phenyl selenoxide
E-12c. A slightly yellow oil. Yield: 0.649 g (93%); IR (neat)
1247, 1021, 845; 31P NMR (81 MHz, CDCl3): d 11.7 ppm;
1H NMR (200 MHz, CDCl3): d 1.22 (t, 6H, JH–HZ7.1 Hz,
CH3CH2OP); 2.15 (dd, 3H, JH–HZ7.3 Hz, JP–HZ3.0 Hz,
CH3C]); 3.4–4.2 (m, 4H, CH3CH2OP); 7.45 (dq, 1H,
JP–HZ41.9 Hz, JH–HZ7.3 Hz, trans C]CH); 7.37–7.85
(m, 5H, aromatic).
3.10.1. a-Diethyl (1-p-tolylsulfinyl)-(2-dimethylamino)-
ethylphosphonate 7e. Cooled dimethylamine (0.5 mL) was
added to 0.3 g (1 mmol) of a-phosphorylvinyl sulfoxide at
0 8C. The reaction mixture was stirred overnight. An excess
of Me2NH was removed affording 7e as a mixture of
diastereomers 2:1 obtained in quantitative yield. 31P NMR
(81 MHz, CDCl3) 21.6/19.8 ppm 1H NMR (200 MHz,
CDCl3): d 1.30 (t, 3H, JZ7.1 Hz, CH3CH2OP); 2.20
(s, 3H, CH3N); 2.22 (s, 3H, CH3N); 2.40 (s, 3H, CH3Ar);
2.74–2.87 (m, 2H, NCH2); 3.08 (td, 1H, JP–HZ17.5 Hz,
JH–HZ6.0 Hz—major); 3.35 (td, 1H, JP–HZ17.9 Hz,
JH–HZ6.2 Hz—minor); 3.97–4.22 (m, 4H, CH3CH2OP);
7.26–7.34 and 7.51–7.62 (m, 4H, aromatic).
Compound Z-12c. Yield: 0.677 g (97%); 31P NMR
(81 MHz, CDCl3) d 12.8 ppm; 1H NMR (200 MHz,
CDCl3): d 1.04 (td, 6H, JH–HZ7.0 Hz, JP–HZ0.5 Hz,
CH3CH2OP); 2.22 (dd, 3H, JP–HZ2.8 Hz, JH–HZ7.3 Hz,
CH3C]); 4.15 (dq, 4H, JP–HZ8.5 Hz, JH–HZ7.0 Hz,
CH3CH2OP); 7.46 (dq, 1H, JH–HZ7.3 Hz, JP–HZ21.2 Hz,
C]CH); 7.22–7.61 (m, 5H, aromatic).
3.10.2. a-Diethyl (1-p-tolylsulfinyl)-(2-methoxy)-ethyl-
phosphonate 7f. To a stirred methanol solution (25 mL)
of 0.3 g (1 mmol) of (S)-(1-diethoxyphosphoryl)vinyl p-
tolyl sulfoxide 0.057 g (1.2 mmol) of NaH (50%) was added
at room temperature. After 2 h of stirring the reaction was
quenched with aqueous solution of NH4Cl, solution was
extracted with chloroform (3!30 mL). The CHCl3 extract
was dried over anhydrous MgSO4 and after evaporation
afforded mixture of diastereomers: 31P NMR (81 MHz,
CDCl3) 19.5/19.4 ppm in 2:1 ratio. Purification by column
chromatography (hexane–acetone 10:1). Yield: 0.25 g
3.8.3. 1-(Diethylphosphoryl)hexenyl phenyl selenoxide
E-12d. A slightly yellow oil. Yield: 0.75 g (96%); 31P NMR
(81 MHz, CDCl3) 12.0 ppm 1H NMR (200 MHz, CDCl3): d
0.78–1.62 (m, 7H); 1.24 (t, 3H, JH–HZ7.0 Hz, CH3CH2OP);
2.55 (m, 2H, CH2C]); 3.4–4.25 (m, 4H, CH3CH2OP); 7.38
(dt, JP–HZ42 Hz, JH–HZ7.9 Hz, CH]); 7.4–7.8 (m, 5H).
3.9. Preparation of alkynylphosphonates 13
The benzene solution (10 mL) of 1 mmol of the selenoxide
12 was heated under reflux for 3 h. After evaporation of
solvent, alkynylphosphonate 13 was purified by distillation
on Kugel Rohr.
1
(75%); H NMR (200 MHz, CDCl3): d 1.24 (t, 6H, JZ
7.1 Hz, CH3CH2OP); 2.40 (s, 3H, CH3Ar); 3.20 (td, 1H,
JP–HZ17.2 Hz, JH–HZ3.6 Hz); 3.34 (s, 3H, CH3O); 3.87–
4.25 (6H, m, CH3CH2OPCCH3OCH2); 7.23–7.36 and
7.57–7.69 (4H, aromatic). 13C NMR (50 MHz, CDCl3):
3.9.1. Diethylphosphorylacetylene 13b. A slightly yellow
oil. Yield: 0.15 g (93%); bp 80–85 8C/10 mm Hg. 31P NMR
(81 MHz, CDCl3): d 7.7 ppm; 1H NMR (200 MHz,
CDCl3)): d 1.38 (td, 6H, JH–HZ7.1 Hz, JP–HZ0.7 Hz,
CH3CH2OP); 2.89 (d, 1H, JP–HZ13.2 Hz), 4.09 (dq, 4H,
JP–HZ8.1 Hz, JH–HZ7.1 Hz CH3CH2OP 13C NMR
(50 MHz, CDCl3): 15.8 (d, 3JZ6.9 Hz); 62.1 (d, 2JZ
6.3 Hz); 70.2 (d, 1JZ307 Hz); 101.0 (d, 2JZ57.1 Hz).
HRMS (70 eV) C6H11O3P requires 162.04458. Found:
162.0459.
3
16.0 (d, JZ4.8 Hz); 21.3; 58.9; 62.6 (d, JZ6.4 Hz); 64.5
(d, JZ138.4 Hz); 65.1 Hz; 125.4; 126.0; 129.4; 141.9. Anal.
Calcd for C14H23O5PS: C, 49.93%; H, 6.91%. Found: C,
49.82%, H, 6.95%.
3.10.3. a-Diethyl (1-p-tolylsulfinyl)-(2,2-dimethyl)-
(2-nitro)-ethylphosphonate 7g. To a stirred THF solution
(50 mL) of 0.3 g (1 mmol) of (S)-(1-diethoxyphosphoryl)-
vinyl p-tolyl sulfoxide 5c sodium salt of 2-nitropropane,
generated by addition 0.057 g (1.2 mmol) of NaH (50%) to
0.12 g of 2-nitropropane in THF solution (15 mL), was
added at 0 8C. The reaction mixture was stirred for 2 h (0 8C
to room temperature) and was quenched with aqueous
solution of NH4Cl. Organic solvents were evaporated and
the remaining aqueous solution was extracted with chloro-
form (2!30 mL). The CHCl3 extract was dried over
anhydrous MgSO4 and evaporated giving mixture of
diastereomers 31P NMR (81 MHz, CDCl3) 21.7/18.5 ppm
3.9.2. Diethyl phosphorylpropyne 13c. A slightly yellow
oil. Yield: 0.142 g (81%); bp 88–92 8C/10 mm Hg 31P NMR
(81 MHz, CDCl3) d 5.7 ppm; 1H NMR (200 MHz, CDCl3):
d 1.35 (td, 6H, JH–HZ7.1 Hz, JP–HZ0.8 Hz, CH3CH2OP);
2.00 (d, 3H, JP–HZ4.7 Hz, CH3C), 4.13 (dq, 4H, JP–H
Z
7.8 Hz, JH–HZ7.1 Hz, CH3CH2OP). 13C NMR (50 MHz,
CDCl3): 4.4 (d, 3JZ4.7 Hz); 16.0 (d, 3JZ7.1 Hz); 61.7
1
2
(2JZ5.9 Hz); 69.9 (d, JZ305 Hz); 98.9 (d, JZ54.7 Hz).
HRMS (70 eV) C7H13O3P requires 176.06023. Found
176.0592.
1
in 2:1 ratio. H NMR (200 MHz, CDCl3): d 1.22 (s, 3H);
1.32 (t, 6H, JZ7.0 Hz, CH3CH2OP); 1.47 (s, 3H); 2.40
(s, 3H, CH3Ar); 2.32–2.6 (m, 2H); 3.03 (major) (ddd, 1H,
JP–HZ17.2 Hz, JH–HZ5.8, 3.4 Hz, PCHS); 3.35 (minor)
(ddd, 1H, JP–HZ20.3 Hz, JH–HZ6.9, 3.6 Hz); 3.95–4.15
3.9.3. Diethyl phosphorylhexyne 13d. A slightly yellow
oil. Yield: 0.207 g (95%); bp 50–55 8C/2 mm Hg 31P NMR

12228
W. H. Midura, J. A. Krysiak / Tetrahedron 60 (2004) 12217–12229
(4H, m, CH3CH2OP); 7.27–7.36 and 7.47–7.64
(4H, aromatic).
temperature, quenched with aqueous NH4Cl (20 mL) and
the product extracted with CHCl3 (3!10 mL). The organic
solution was dried over MgSO4, solvent evaporated and the
product 16 purified by column chromatography (hexane–
acetone 18:1). Yield: 0.628 g (65%); IR(neat) 1729, 1252,
3.10.4. a-Diethyl (1-p-tolylsulfinyl)-(2,2-dicarboethoxy)-
ethylphosphonate 7h. To a stirred THF solution (50 mL) of
0.3 g (1 mmol) of (S)-(1-diethoxyphosphoryl)vinyl p-tolyl
sulfoxide 5c lithium salt of diethyl malonate, generated by
addition 0.016 g (2 mmol) of LiH to 0.19 g of diethyl
malonate in THF solution, was added at 0 8C. The reaction
mixture was stirred for 2 h (0 8C to room temperature) and
was quenched with aqueous solution of NH4Cl. Organic
solvents were evaporated and the remaining aqueous
solution was extracted with chloroform (2!30 mL). The
CHCl3 extract was dried over anhydrous MgSO4 and
evaporated giving mixture of diastereomers: 31P NMR
(81 MHz, CDCl3) 21.6/18.9 ppm in 2:1 ratio, purified by
column chromatography (hexane–acetone 10:1). Yield:
0.41 g (88%); 1H NMR (200 MHz, CDCl3): d 1.1–1.38
(m, 12H, CH3CH2OPCCH3CH2OC); 1.38–1.79 (m, 2H);
2.37 (s, 3H, CH3Ar); 3.16 (major) (td, 1H, JP–HZ17.4 Hz,
1
1044; 31P NMR (81 MHz, CDCl3) d 24.3 ppm; H NMR
(200 MHz, CDCl3): d 1.26 (t, 6H, JZ7.1 Hz, CH3CH2OP);
1.29 (t, 3H, JH–HZ7.0 Hz, CH3); 1.31 (t, 3H, JH–HZ7.0 Hz;
2.36 (s, 3H, CH3C]); 3.37 (d, 2H, JZ24.9 Hz, PCH2C]);
3.93–4.32 (m, 4H, CH3CH2OP).
2-Nitropropane. To a solution of 2-nitropropane (1 mmol)
in 30 mL THF potassium t-butoxide (1 mmol) was added at
room temperature and the mixture was stirred for 30 min.
Then the phosphoryl selenoxide E-12c (1 mmol) was added
and this mixture was stirred at room temperature for the next
0.5 h. The reaction was quenched with aqueous NH4Cl
(10 mL) and the product extracted with CHCl3 (3!10 mL).
The organic solution was dried over MgSO4, solvent
evaporated giving mixture of two products 17 and 18 in
about 1:1 ratio, defined by 31P NMR spectra. Both products
were separated by column chromatography (benzene/
acetone).
JH–HZ7.2 Hz); 3.47 (minor) (td, 1H, JH–HZ7.4 Hz, JP–H
Z
14.4 Hz); 3.63 (major) (t, 1H, JH–HZ7.1 Hz); 3.87 (minor)
(t, 1H, JH–HZ7.1 Hz); 3.87–4.21 (m, 8H, CH3CH2OPC
CH3CH2OC); 7.25–7.36 (m, 2H, aromatic) and 7.47 (major)
and 7.64 (minor) (4H, aromatic). Anal. Calcd for
C14H31O8PS: C, 51.94%; H, 6.76%. Found: C, 51.79.%,
H, 6.95%.
3.13.2. Diethyl (2,3-dimethyl)(3-nitro) buten-1 phospho-
nate 17. A pale yellow oil. Yield: 0.11 g (42%); IR (neat)
1241, 1050, 1025; 31P NMR (81 MHz, CDCl3): d 16.8 ppm;
1H NMR (200 MHz, CDCl3): d 1.33 (t, 6H, JH–HZ7.0 Hz,
CH3CH2OP);1.74(s, 6H, CH3CN); 2.08(dd, 3H, JH–HZ1 Hz,
3.11. Reaction of vinyl selenide 11c with Me2NH
JP–HZ3.3 Hz, CH3C]); 4.10 (dq, 4H, JP–HZ8.1 Hz, JH–H
7.0 Hz, CH3CH2OP); 5.73 (dq, 1H, JP–HZ13.4, JH–HZ1 Hz).
Z
Cooled dimethylamine was added to a-phosphorylvinyl
selenide 11c (0.23 g, 1 mmol) at 0 8C. The reaction mixture
was stirred overnight. An excess of Me2NH was removed
and residue was a mixture of diastereomers of 14 obtained
in quantitative yield, 31P NMR (81 MHz, CDCl3) 26.6/
26.7 ppm.
3.13.3. Diethyl 1-propen-3-ol phosphonate 18c. Yield:
0.087 g (45%); 31P NMR (81 MHz CDCl3) d 19.5 ppm; 1H
NMR (200 MHz CDCl3): d 1.28 (t, 6H, JH–HZ7.1 Hz,
CH3CH2OP); 2.93 (m, 1H, OH); 4.03 (dq, 4H, JH–H
Z
7.1 Hz, JP–HZ7.7 Hz CH3CH2OP); 4.22 (m, 2H, CH2OH);
5.95 (tdd, 1H, JH–HZ2.1, 17.2 Hz, JP–HZ21.3 Hz, PCH]);
6.8 (tdd, 1H, JH–HZ3.6, 17.2 Hz, JP–H Z22.6 Hz, CH]).
From Z-11—ratio 2:1 from E-11—ratio 10:1. 1H NMR
(200 MHz, CDCl3): d 1.25–1.34 (9H, m, CH3CH2OPC
CH3C); 2.22 and 2.25 (2!s, 6H, CH3N); 3.07–3.17 (m, 1H,
CHN); 3.22 (dd, 1H, JP–HZ17.9 Hz, JH–HZ3.8 Hz,
PCHSe); 4.02–4.29 (m, 4H, CH3CH2OP); 7.23–7.69
(m, 5H, aromatic).
Overhauser effect of 17. Irradiation of the vinyl proton
(d 5.73 ppm) caused 21% increasing of signal 2.08
(dd, CH3). Irradiation of the methyl protons (d 2.08 ppm)
caused a 17% enhancement of signal 5.73 (dq, ]CH).
3.12. Oxidation of phosphonate 14
3.13.4. Diethyl 1-hexen-3-ol phopsphonate 18d. Yield:
0.18 g (76%); [a]DZC8.1 (c 0.5, acetone), 31P NMR
(81 MHz, CDCl3); d 19.8 ppm; 1H NMR (200 MHz,
CDCl3): d 0.91 (t, 3H, JZ7.2 Hz, CH3CH2); 1.30 (t, 6H,
JZ7.0 Hz, CH3CH2OP); 1.2–1.6 (m, 4H); 2.63 (m, 1H,
OH); 4.05 (dq, 4H, JH–HZ7.0 Hz, JP–HZ8.2 Hz, CH3CH2-
OP); 4.25 (m, 1H, CHOH); 5.90 (ddd, 1H, JH–HZ17.1,
1.7 Hz, JP–HZ21.0 Hz, PCH); 6.77 (ddd, 1H, JH–HZ17.1,
4.2 Hz, JP–HZ22.4 Hz, CH]).
To a solution of adduct 14 (mixture of diastereomers) in
CH2Cl2 mixture of 30% H2O2 and water (1:1) was added at
(a) K20 8C, (b) room temperature. The reaction was stirred
for 0.5–1 h at appropriate temperature yielding mixture of
products where b-ketophosphonate 15 (a) or a-phos-
phorylvinyl selenoxide E-12 (b) as major ones. In both
cases E-12 and 15 were separated by chromatography.
3.13. Nucleophilic addition to a-phosphorylpropenyl
phenyl selenoxide 12c
3.13.1. Diethyl malonate. To a solution of 3 mmol of
diethyl malonate in 20 mL THF, 0.16 g (3.3 mmol) of
sodium hydride 50% in oil was added at room temperature.
After 30 min the reaction mixture was cooled down to
K78 8C and vinyl selenoxide E-12c (3 mmol) was added.
The stirred reaction mixture was warmed up to room
References and notes
1. Minami, T.; Motoyoshiya, J. Synthesis 1992, 333–349.
2. Mikołajczyk, M.; Bałczewski, P. Top. Curr. Chem. 2003, 223,
161–214.

W. H. Midura, J. A. Krysiak / Tetrahedron 60 (2004) 12217–12229
12229
3. Mastalerz, P. In Handbook of Organophosphorus Chemistry;
Engel, R., Ed.; Marcel Dekker: New York, 1992; Chapter 7,
p 277.
13. This hypothesis was recently supported by X-ray analysis of
1-diphenylphosphinoylvinyl p-tolyl sulfoxide, where a hydro-
gen bond between vinyl proton and sulfinyl oxygen with the
˚
distance 2.305 (30) A was found. Midura, W. H.; Krysiak, J.
4. Venugopalan, B.; Hamlet, A. B.; Durst, T. Tetrahedron Lett.
1981, 22, 191–194.
A.; Cypryk, M.; Mikołajczyk, M.; Wieczorek, M. W.;
Filipczak, A. D. Eur.J. Org. Chem., in press.
5. Gulea, M.; Masson, S. Top. Curr. Chem. 2003, 229, 161–198.
6. Midura, W. H.; Krysiak, J. A.; Wieczorek, M. W.; Majzner,
W. R.; Mikołajczyk, M. Chem. Commun. 1998, 1109–1110.
Midura, W. H.; Krysiak, J. A.; Mikołajczyk, M. Tetrahedron
1999, 55, 14791–14802.
14. Midura, W. H.; Mikołajczyk, M. Tetrahedron Lett. 1995, 36,
2871–2874.
15. Sulfoxide 50e was prepared from (C)-(S)-dimethoxyphos-
phorylmethyl p-tolyl sulfoxide according to the procedure
described in our recent paper: Midura, W. H.; Mikołajczyk, M.
Tetrahedron Lett. 2002, 43, 3061–3065.
7. Mikołajczyk, M.; Midura, W. H. Tetrahedron: Asymmetry
1992, 3, 1515–1518. Midura, W. H.; Krysiak, J. A.;
Mikołajczyk, M. Tetrahedron: Asymmetry 2003, 14,
1245–1249.
16. Annunziata, R.; Cinquini, M.; Cozzi, F.; Raimondi, L.;
Rastelli, A. Gazz. Chim. Ital. 1985, 115, 637–641. Nokami,
J.; Mandai, T.; Nishimura, A.; Takeda, T.; Wakabayashi, S.;
Kunieda, N. Tetrahedron Lett. 1986, 27, 5109–5112. Kosugi,
H.; Kitaoka, A.; Takahashi, A.; Uda, H. Chem. Commun. 1986,
56, 1268–1270.
8. Liotta, D.; Zima, G.; Barnum, Ch.; Saindane, M. Tetrahedron
Lett. 1980, 21, 3643–3646.
9. Mikołajczyk, M.; Grzejszczak, S.; Korbacz, K. Tetrahedron
Lett. 1981, 22, 3097–3100.
´
10. (a) Mikołajczyk, M.; Kiełbasinski, P.; Grzejszczak, S.
17. Dominguez, E.; Carretero, J. C. Tetrahedron 1990, 46,
7197–7206. Trost, B. M.; Mallart, S. Tetrahedron Lett. 1993,
34, 8025–8028. Guerrero-de la Rosa, V.; Ordonez, M.;
Alcudia, F.; Llera, J. M. Tetrahedron Lett. 1995, 36,
4889–4892.
Synthesis 1983, 332–334. (b) Mikołajczyk, M.; Bałczewski,
P. Synthesis 1989, 101–106.
11. Mikołajczyk, M.; Midura, W.; Grzejszczak, S.; Zatorski, A.;
´
Chefczynska, A. J. Org. Chem. 1978, 43, 473–478.
Mikołajczyk, M.; Midura, W.; Miller, A.; Wieczorek, M. W.
Tetrahedron 1987, 43, 2967–2976.
18. Nokami, J.; Taniguchi, A.; Honda, M.; Fukutake, S. Chem.
Lett. 1995, 1025–1026.
12. Reetz, M. T.; Peter, R.; Von Itzstein, M. Chem. Ber. 1987, 120,
121–124.