Study of the addition of monoalkylphosphonic acids onto trialkyl-substituted epoxides

Article abstract of DOI:10.1021/jo001453p

The addition of 2-chloroethylphosphonic acid (or ethephon), a well-known stimulating molecule for the production of latex by Hevea brasiliensis, onto 2,3-epoxy-2-methylbutane was investigated to enhance the understandings on the addition mechanisms of reagents of alkylphosphonic acid type onto trialkyl-substituted epoxides. It was demonstrated that the addition occurs according to a three-step mechanism including a rapid nucleophilic attack of the phosphorated anion on the most alkyl-substituted carbon of the oxirane, followed by formation of a dioxaphospholane structure with release of water, and finally a hydrolytic cleavage of the dioxaphospholane cycle to generate the regioisomer 1:1 adduct where the phosphorated group is on the less alkyl-substituted carbon of the initial oxirane.

Full text of DOI:10.1021/jo001453p

J . Org. Chem. 2001, 66, 3767-3774
3767
Stu d y of th e Ad d ition of Mon oa lk ylp h osp h on ic Acid s on to
Tr ia lk yl-Su bstitu ted Ep oxid es
Daniel Derouet,* Laurent Cauret, and J ean-Claude Brosse
L.C.O.M. Chimie des Polyme`res (Unite´ Mixte de Recherche du CNRS LCO2M No. 6011),
Universite´ du Maine, Avenue Olivier Messiaen, F-72085 Le Mans Cedex 9, France
Daniel.Derouet@univ-lemans.fr
Received October 9, 2000
The addition of 2-chloroethylphosphonic acid (or ethephon), a well-known stimulating molecule for
the production of latex by Hevea brasiliensis, onto 2,3-epoxy-2-methylbutane was investigated to
enhance the understandings on the addition mechanisms of reagents of alkylphosphonic acid type
onto trialkyl-substituted epoxides. It was demonstrated that the addition occurs according to a
three-step mechanism including a rapid nucleophilic attack of the phosphorated anion on the most
alkyl-substituted carbon of the oxirane, followed by formation of a dioxaphospholane structure with
release of water, and finally a hydrolytic cleavage of the dioxaphospholane cycle to generate the
regioisomer 1:1 adduct where the phosphorated group is on the less alkyl-substituted carbon of
the initial oxirane.
In tr od u ction
hindrance and the nature of substituents of the oxirane
ring: for instance, in the case of 1,2-epoxy-2-methylpro-
The addition of organophosphorated reagents onto
oxirane rings by the intermediate of P-OH functions
does not necessitate the use of a catalyst. A kinetic study
of the addition of dihydroxyethylphosphoric acid onto
ethylene oxide showed that, without catalyst, the addition
is autocatalyzed by the acid functions P-OH of the
reagent.1 The activation of the oxirane ring is due to the
formation of a hydrogen-type bond2 between the oxirane
oxygen and the acid function of the reagent (eq 1), which
increases the electrophilicity of the oxirane ring.
pane, the â-addition is favored3.
Moreover, it was noticed that the 1:1 addition is dis-
turbed by secondary reactions, which can lead to the
formation of dioxaphospholane and diol derivatives3 (eqs
3 and 4).
The previous studies concerning this field of research
showed that the addition on terminal epoxides is not
regioselective: the opening of the oxirane ring occurs
either in the R or in the â position. It was noticed in the
case of propylene oxide (studies realized with dieth-
ylphosphoric acid, phosphorous acid, and phosphoric
acid)3 (eq 2) that the relative proportions in 1:1 adducts,
resulting from oxirane ring opening in R or â, are
independent of the functionnality of the phosphorated
reagent (mono-, di-, or triacid), of the temperature and
of the nature of solvent. Whatever the organophosphor-
ated reagent, the regioisomer ratio calculated from the
As part of the research realized in the field of chemical
modification of epoxidized 1,4-polyisoprene by 2-chloro-
ethylphosphonic acid (or ethephon) 1,4 it was decided to
investigate the reaction of this reagent onto 2,3-epoxy-
2-methylbutane 2. The synthesis of 1,4-polyisoprenes
support of 1 was considered in order to prepare systems
able to allow a controlled release of 1 during the time (1
is linked to the polymer backbone by a hydrolyzable
bond), with the objective to prolong the stimulating
activity of 1 for latex production by Hevea brasiliensis.5
Compound 2 was chosen the first time, as a model
molecule of epoxidized 1,4-polyisoprene unit, to facilitate
1
intensities of the H or 31P NMR respective signals3 is
always about 50/50 (eq 2). On the other hand, the
orientation of the addition can be influenced by the steric
(1) Biela, T.; Kubisa, P. Makromol. Chem. 1991, 192, 473.
(2) Biela, T.; Szymanski, R.; Kubisa, P. Makromol. Chem. 1992, 193,
285.
(3) Biela, T.; Kubisa, P.; Penczek, S. Makromol. Chem. 1992, 193,
1147.
(4) Submitted to Eur. Polym. J .
10.1021/jo001453p CCC: $20.00 © 2001 American Chemical Society
Published on Web 04/27/2001

3768 J . Org. Chem., Vol. 66, No. 11, 2001
Derouet et al.
1
F igu r e 1. 1H NMR spectrum of the crude mixture (CDCl3, δ in ppm), compared with H NMR spectra of initial products 1 and 2.
the identification and the characterization of the various
phosphorated adducts and secondary products formed
during the reaction. The purpose of this paper is to
enhance the understandings on the addition mechanisms
of reagents of alkylphosphonic acid type onto the epox-
ides, for instance, in the present case, the trialkyl-
substituted epoxides.
spectrum (Figure 2). According to the measures realized
1
from the H and 31P NMR spectra, only 43% (1H NMR)
[54% (31P NMR)] of 1 is transformed. This result is
explained by the existence of secondary reactions that
lead to the transformation of part of the initial epoxide
in nonphosphorated derivatives, which are also charac-
1
terized by H NMR.
An a lysis a n d Ch a r a cter iza tion of th e P h osp h or -
a t ed Ad d u ct s F or m ed . By reference to the works of
Biela et al.,1-3 it was initially established that the
following phosphorated adducts could be formed: the
regioisomers 3 and 4 (1:1 adducts) issued from the
addition of 1, respectively, in the R and â positions on
the oxirane ring of 2 (eq 5), and the dioxaphospholane 5
issued of 3 or 4 after elimination of water6 (eq 6).
Resu lts a n d Discu ssion
To better understand the reaction between 2-chloro-
ethylphosphonic acid 1 and 2,3-epoxy-2-methylbutane 2,
convenient reaction conditions were selected to obtain
simultaneously a good representation of the different
products (1:1 adducts and secondary derivatives) formed
during the reaction. For that, the reaction between acid
1 and epoxide 2 in equimolecular quantities was carried
out at 20 °C, in the absence of solvent.
The crude mixture obtained after 24 h of stirring was
1
1
analyzed by H NMR and then by 31P NMR. H NMR
analysis of the crude mixture (Figure 1) shows a total
disappearance of the triplet at 2.85 ppm (oxirane ring
protons) which indicates a complete transformation of the
epoxide, even though ethephon 1 (CDCl3, δ ) 27.2 ppm)
is not totally consumed as shown also on the 31P NMR
(5) (a) Audley, B. G.; Archer, B. L. Chem. Ind. London 1973, 634.
(b) Audley, B. G. Phytochemistry 1979, 18, 53. (c) Mayard, J . A.; Swan,
J . M. Aust. J . Chem. 1963, 16, 596. (d) Kays, S. J .; Beaudry, R. M.
Acta Horticulturae 1987, 201. (e) Biddle, E.; Kerfoot, D. G. S.; Hwa
Kho, Y.; Russell, K. E. Plant Physiol. 1976, 58, 700.

Study of the Addition of Monoalkylphosphonic Acids
J . Org. Chem., Vol. 66, No. 11, 2001 3769
the formation of two diastereomers R,R (or S,S) and R,S
(or S,R) (Figure 3) explained by the existence of two
asymmetric centers in the molecule (a carbon and the
phosphorus).8
The existence of the two dioxaphospholane diastereo-
mers is also confirmed by the analyses realized in 13C
1
and H NMR. In 13C NMR, the carbons ClCH2, CHOP,
and COP are all characterized by two singlets, and the
carbon CH2P by two doublets explained by the coupling
with the phosphorus atom. Moreover, six peaks (singlets)
characteristic of the methyl groups are noticed between
1
δ ) 15 ppm and δ ) 26 ppm. In H NMR (CDCl3) (Figure
4), two doublets of quadruplets are noticed for the CHOP
protons respectively at δ ) 4.54 and 4.32 ppm (coupling
3
3
3
constants: J HP ) 2.1 Hz and J HH ) 6.4 Hz; J HP ) 1.9
3
Hz and J HH ) 6.4 Hz). The methyl protons are charac-
terized by four singlets (δ ) 1.31, 1.55, 1.42, and 1.48
ppm) and two doublets at δ ) 1.39 ppm (3J HH ) 6.4 Hz)
and δ ) 1.33 ppm (3J HH ) 6.4 Hz).
The relative proportions in 5a and 5b in the crude
mixture were calculated from the 31P NMR spectrum by
comparing the intensities of the respective signals: [5a ]/
[5b] ) 0.56.
To complete the characterization of 5a and 5b (see the
Experimental Section), the 2D H-H (and H-C) NMR
and proton selective irradiation were used. By these
means, it was demonstrated that the doublets of qua-
druplets characteristic of the CHOP protons at δ ) 4.54
ppm and δ ) 4.32 ppm were coupled with the doublets
characteristic of the methyl protons respectively at δ )
1.33 and 1.39 ppm. Moreover, the analysis by 2D C-H
NMR allowed to identify the chemical shifts of the
methyls MeCHOP and (Me)2COP knowing their attribu-
F igu r e 2. 31P NMR spectrum of the crude mixture (CDCl3, δ
in ppm).
The various 1:1 adducts formed during the reaction are
1
identified in H NMR by three signals at, respectively, δ
) 4.32, 4.42, and 4.54 ppm (Figure 1), characteristic of
CHOP protons corresponding to each phosphorated ad-
duct formed.
1
tion in H NMR.
The analysis by 31P NMR (Figure 2) shows four peaks
at δ ) 39.2, 39.1, 26.5, and 24.3 ppm characteristic of
four phosphorated adducts. The proportion of these
adducts determined by 31P NMR represents about 48%
of the organophosphorated compounds contained in the
crude mixture obtained after 24 h of reaction. Residual
ethephon is also noticed at δ ) 27.2 ppm (∼46% of the
phosphorated compounds), which demonstrates that the
addition is accompanied by secondary reactions because
the starting epoxide is totally transformed. The small
peaks identified betwen δ ) 22 and 23 ppm indicate the
presence of a low proportion of secondary phosphorated
derivatives (≈ 6%).
Knowing that electronegative atoms, such as oxygen,
cause deshielding of hydrogen atoms and taking into
3
account the fact that very low values of the J PHOCH
indicate a low dihedral angle P-O-C-H, which is the
case in the present diastereomers (see above), it was
1
possible to give a complete H NMR characterization for
the diastereomers 5a and 5b. Thus, the signal of the
CHOP proton in the diastereomer S,R (or R,S), which is
sterically closer to the oxygen atom of the PdO bond than
in the case of the diastereomer S,S (or R,R), corresponds
to the chemical shift at the lowest field (δ ) 4.54 ppm).
According to a similar approach, the chemical shifts of
the various methyls could be identified leading to the
conclusion that for the methyls a and b, the higher
chemical shift corresponds to the methyls of the diaste-
reomer R,R (or S,S) and for the methyls c, to the methyl
of the diastereomer R,S (or S,R).
According to the literature,3 the addition on epoxides
is nonregioselective: the two other phosphorated adducts
characterized on the 31P NMR spectrum of the crude
mixture (Figure 2), respectively, at 26.5 ppm (high peak)
and 24.3 ppm (very small peak) can be attributed to the
two regioisomers 3 and 4. The difference of peaks
intensities seems to indicate that the addition on trialkyl-
substituted epoxides would be quasi regioselective.
The regioisomer mainly formed was characterized in
1H NMR as being 3. After subtraction of the signals
The formation of dioxaphospholane 5 was confirmed
1
after comparison of the H, 31P, and 13C NMR spectra of
the crude mixture with those of the dioxaphospholane
prepared at low temperature by reaction between 2-chlo-
roethylphosphonyldichloride and 3-hydroxy-2-methylbu-
tan-2-ol 8 (eq 7), in a nonpolar solvent (benzene) and in
the presence of 2,6-dimethylpyridine to neutralize the
HCl formed.7
The dioxaphospholane is characterized in 31P NMR by
two peaks at δa ) 39.27 ppm and δb ) 39.1 ppm due to
(7) Fontaine, L.; Derouet, D.; Brosse, J . C. Eur. Polym. J . 1990, 26,
857.
(6) Klosinsky, P.; Penczek, S. Makromol. Chem., Rapid Commun.
1988, 9, 159.
(8) Biela, T.; Klosinski, P.; Penczek, S. J . Polym. Sci, Part A: Polym.
Chem. 1989, 27, 763.

3770 J . Org. Chem., Vol. 66, No. 11, 2001
Derouet et al.
F igu r e 3. Diastereomer 5a and 5b of the dioxaphospholane 5.
F igu r e 4. 1H NMR spectrum of the dioxaphospholane diastereomers obtained from the reaction between 2-chloroethylphospho-
nyldichloride and 8.
1
F igu r e 5. Characterization of 3 by H NMR (CDCl3, δ in ppm).
characteristic of dioxaphospholane protons of 5, it was
possible to notice on the H NMR spectrum of the crude
Figure 6. The other regioisomer 4 was not identified on
the 1H NMR spectrum of the crude mixture analyzed
after 24 h of reaction: normally, a signal characteristic
of the CHOH proton should be noticed around δ ) 3.5
ppm.
Ch a r a cter iza tion of Secon d a r y Der iva tives. Three
secondary products derived from 2 were identified: a
ketone, an allylic alcohol, and an R,â-diol (Figure 7). They
were characterized on the 1H NMR spectrum of the crude
1
mixture (Figure 5) at δ ) 4.42 ppm, a doublet of qua-
druplets characteristic of the P-O-CH(Me)-C proton of
3
3 (3J HH ) 6.45 Hz, J HP ) 8.8 Hz), and also a doublet at
δ ) 1.27 ppm (3J HH ) 6.45 Hz) for the protons of the
methyl POCH(Me)C and two singlets at δ ) 1.19 and 1.17
1
ppm for that of the methyls (Me)2COHC-. The H, 31P,
and 13C NMR characteristics of 3 are summarized in

Study of the Addition of Monoalkylphosphonic Acids
J . Org. Chem., Vol. 66, No. 11, 2001 3771
phorated 1:1 adducts 3 and 4, versus time (the secondary
phosphorated derivatives were taken into account in the
calculation of the proportions, but they are not repre-
sented on the graphs).
These graphs show, as well without solvent as in
chloroform, that the reaction is excessively fast since a
significant ethephon consumption, about 50%, is observed
immediatly after the start of the reaction. Thereafter, the
ethephon consumption does not progress any more, which
is explained by the rearrangement reactions of part of
the oxirane rings (the increase of ethephon content of
about 10%, which is noticed during the first 30 min of
the reaction carried out in chloroform is probably due
to the hydrolysis of part of the phosphorated 1:1 ad-
ducts according to eq 9). It is especially significant to
note that it is the regioisomer 4, that is the 1:1 adduct
with the phosphorated group fixed on the most substi-
tuted carbon of the oxirane, which really results from
the addition of 1 onto 2, whereas this same regioisomer
is not present after 24 h of reaction. It is also impor-
tant to specify that the totality of 1 is consumed during
the first minutes of the reaction, which explains why
the proportion of residual ethephon remains almost
constant thereafter, this proportion corresponding to that
of 1 transformed in nonphosphorated secondary deriva-
tives.
F igu r e 6. 1H, 31P, and 13C NMR characteristics of 3 (CDCl3,
δ in ppm).
F igu r e 7. Secondary products derived from 2 obtained during
the reaction of 1 with 2.
mixture (Figure 1) from their specific chemical shifts
beforehand obtained from the bibliography (in the case
of 6 and 79) or after synthesis of the compound (in the
case of 8 prepared by addition of water onto 2 catalyzed
by cerium ammonium nitrate10).
The secondary derivatives that represent about 51%
of the compounds obtained from 2 are distributed as
follows: 43.6% of 8, 5.5% of 7, and 1.8% of 6 (determined
from the intensities of the respective characteristic
signals noticed on the 1H NMR spectrum). Consequently,
only 49% of 2 was really transformed in phosphorated
adducts.
Kin etic Stu d y of th e Ad d ition of 1 on to 2. The
evolution of the reactional mixture composition versus
time was followed by 31P NMR, by comparing the intensi-
ties of the various peaks characteristic of the phospho-
rated products present in the mixture. To stop the
reaction, each sample was plunged into a bath main-
tained at -40 °C until NMR analyses that were also
carried out at low temperature (-20 °C).
Thereafter, an evolution of the mixture composition in
1:1 phosphorated adducts formed is noticed since the
initially formed regioisomer 4 disappears gradually to
reach a final proportion of 5%. At the same time, the
dioxaphospholanes 5 and the regioisomer 3 appear within
the first seconds of the reaction. As the global proportion
in dioxaphospholanes increases during the first 2 h and
then decreases, that of the regioisomer 3 follows a
constant increase during the time to reach respectively
30% after 8 h of reaction in CDCl3 and 25% without
solvent.
Consequently, the formation of the dioxaphospholanes
5 and afterward, that of the 1:1 adduct 3 in which the
phosphorated entity is on the less substituted carbon of
the oxirane ring, would be the result of several successive
conversions from the regiosiomer 4 initially formed.
Because the proportions of dioxaphospholane adducts 5
decrease after 2 h of reaction, it was deduced that the
formation of the regiosiomer 3 observed after long dura-
tions of reaction occurred from the dioxaphospholane
intermediate.
The kinetic studies were realized without solvent
(Figure 8, graph A) and then in CDCl3 (Figure 8, graph
1
B). H and 31P NMR spectra were obtained in CDCl3.
The analysis of the 31P NMR spectra of samples taken
at different times showed the presence of four main
phosphorated adducts, that is one more than in the final
mixture after 24 h of reaction. The secondary phospho-
rated derivatives also formed during the addition of 1
onto 2 are minority (∼10% of the totality of the organo-
phosphorated compounds for the reaction carried out in
the absence of solvent and ∼5% for that carried out in
chloroform).
From these results, a mechanism was suggested (Fig-
ure 10). The addition of ethephon on the epoxides would
occur according to the following way. Initially, after acid
activation of the oxirane ring, a regioselective binding of
the phosphorated group on the most hindred carbon of
the oxirane ring, that is the most stable carbocation, leads
to the 1:1 adduct 4. Thereafter, 4 gives the dioxaphos-
pholane 5 by elimination of a molecule of water.6 The
dioxaphospholane adduct 5, very sensitive to acid hy-
drolysis, can then generate the regioisomer 3 which is
more stable than 4 (Figure 10).
The 31P NMR analysis of the sample taken immediatly
after the start of the reaction was surprising because it
revealed the instantaneous formation of high proportions
of the regioisomer corresponding to the fixation of the
phosphorated group on the more substituted carbon of
the oxirane, that is 4 (Figure 9). Until now, the adduct 4
was not identified in the crude mixtures characterized
after 24 h of reaction, because it is immediately trans-
formed into dioxaphospholane.
The secondary reactions can be easily explained ac-
cording to the acidity of the reaction medium and the
presence of water formed in situ during the cyclization
step which leads to the dioxaphospholane structure
(Figure 10). The ketone 6 and the allylic alcohol 7 result
from a rearrangement of the epoxide, a well-known
reaction that can occur in acid medium11-13 (eq 8). The
The kinetic curves (Figure 8) show the evolution of the
contents in ethephon 1, dioxaphospholanes 5, 1:1 phos-
(9) Pouchet, C. J .; Behnke, J . The Aldrich Library of 13C and 1H
NMR, 1993.
(10) Iranpoor, N.; Baltork, I. M.; Zardaloo, F. S. Tetrahedron 1991,
47(47), 9861.

3772 J . Org. Chem., Vol. 66, No. 11, 2001
Derouet et al.
F igu r e 8. Kinetic study of the addition of 1 onto 2, respectively, without solvent (graph A) and in CDCl3 (graph B).
study, it is probable that it results from the hydrolysis
of the C-O-P bond of 4 (eq 9).
In summary, we have found that the addition of
2-chloroethylphosphonic acid 1 onto trialkyl-substituted
oxirane rings occurs with formation of two categories of
F igu r e 9. 1H and 31P NMR characteristics of 4 (CDCl3, δ in
products: (1) organophosphorated adducts of type 1:1
ppm).
adduct and dioxaphospholane (formation of diastereo-
mers), issued from the addition of 1 on the oxirane of 2;
origin of the R,â-diol 8 is more uncertain. However,
(2) nonphosphorated derivatives including allylic alcohol
thanks to the information obtained from the kinetic
and ketone (formed by rearrangement of 2) and R,â-diol
(probably issued from the acid hydrolysis of the phos-
phorated 1:1 adduct formed in first).
(11) Zon, A. V.; Huis, R. J . Royal Netherlands Chem. Soc. 1981, 100,
425.
(12) Maruoka, K.; Bureau, R.; Ooi, T.; Yamamoto, H. Synlett. 1991,
491.
(13) Smith, J . G. Synthesis 1984, 629.
From the kinetic study of the addition of 1 onto 2, it
was possible to understand the various mechanisms that

Study of the Addition of Monoalkylphosphonic Acids
J . Org. Chem., Vol. 66, No. 11, 2001 3773
F igu r e 10. Mechanism of the addition of 1 onto 2.
recorded on a Bruker AC 400 (400.13, 100.62, and 161.98 MHz,
respectively) in CDCl3. Chemical shifts (δ) are expressed in
ppm downfield from tetramethylsilane (TMS) as internal
standard [H3PO4 in 31P NMR], and coupling constants are
reported in hertz. 2D 1H/13C correlated spectroscopy was
performed on a Bruker DPX 200 Fourier transform spectrom-
eter operating at 200.13 MHz for 1H and at 50.32 MHz for
13C, by using the XH-CORR Bruker program. Fractionations
by semipreparative HPLC were realized with a Waters Delta
Prep 3000 apparatus equipped with a µBondapack C18 column
(19 mm i.d. and 15 cm in length; particle size: 10 µm) and a
Waters R 401 differential refractometer detector. IR spectra
were recorded on a Fourier transform Perkin-Elmer 1750
spectrometer in the 4000-500 cm-1 range (liquid films samples
between two KBr or NaCl cells).
Ep oxid a tion of 2-Meth yl-2-bu ten e. A 39.7 mmol portion
of 2-methyl-2-butene in 100 mL of dichloromethane was
introduced in a round-bottomed flask equipped with a mag-
netic stirrer and a dropping funnel. The reactor was placed in
a bath thermostated at 0 °C. Then, a solution of 52.9 mmol
(9.12 g) of m-chloroperbenzoic acid (75% purity) in 100 mL of
dichloromethane was slowly added. After 6 h of stirring, the
m-chlorobenzoic acid formed was removed by filtration. The
filtrate was washed with an aqueous solution of 10% Na2S2O3
to eliminate the peracid excess, a solution of NaHCO3 (5%),
then with distilled water until neutral pH. Afterward, the
organic layer was dried on anhydrous magnesium sulfate.
After filtration and evaporation of dichloromethane in a
are involved during the reaction and, especially, to
highlight that the formation of the 1:1 adduct 3 with the
phosphorated group on the less substituted carbon of the
initial oxirane is the result of several chemical conver-
sions starting from the regiosisomer 4 formed instanta-
neously after the start of the reaction.
vacuum, the epoxidized product 2 was isolated by distillation
1
[Eb(760
) 70 °C], yield ) 40%. Characterization of 2: H
mmHg)
NMR (CDCl3) δ 1.27 (d; CH3 on the CH of the oxirane ring),
1.28 and 1.31 (2 s; CH3 on the C of the oxirane ring), 2.85 (q;
CH of the oxirane ring); 13C NMR (CDCl3) δ 13.93 (s; CH3 on
the CH of the oxirane ring), 18.18 and 24.45 (2 s; CH3 on the
C of the oxirane ring), 53.13 (s; CH of the oxirane ring), 57.84
16
Exp er im en ta l Section
(s; C of the oxirane ring); IR (KBr; cm-1
)
2964 (ν CH), 1461
(asym), 1378 (sym) (δ CH), 1255 (ν PdO), 860 (δ CO).
Gen er a l Ma t er ia ls a n d Met h od s. 2-Methyl-2-butene 2
(98% purity) was purchased from Aldrich Chemical Co and
used without further purification, as well as deuterated
chloroform-d (99.8% purity; Spectrome´trie Spin et Techniques).
2-Chloroethylphosphonic acid 1 was prepared according to the
method previously described.14,15 All other reagents were
obtained from commercial sources and were used without
further purification. 1H, 13C, and 31P NMR spectra were
Ad d ition of 1 on to 2. Equimolecular quantities of 1 and 2
(1.38 mmol of each reagent) were placed in a 10 mL Pyrex
glass tube equipped with a magnetic stirrer and closed by a
screwed stopper with a joint of sealing covered with Teflon.
The reaction was carried out without solvent and then in
CDCl3. The reaction mixture was stirred at 20 °C for 24 h and
then analyzed by NMR.
Syn th esis of th e Dioxa p h osp h ola n e (5). A 1.08 mmol
portion of 8 and 2.16 mmol of 2,6-dimethylpyridine in 5 mL of
(14) Cauret, L.; Brosse, J . C.; Derouet, D.; de Livonnie`re, H. Synth.
Commun. 1997, 27, 647.
(15) Cauret, L.; Brosse, J . C.; Derouet, D.; de Livonnie`re, H. Bull.
Soc. Chim. Fr. 1997, 463.
(16) Socrates, G. Infrared Characteristic Group Frequencies; J ohn
Wiley & Sons Ltd.: New York, 1980.

3774 J . Org. Chem., Vol. 66, No. 11, 2001
Derouet et al.
benzene were placed, under nitrogen atmospohere, in a round-
Syn th esis of 2,3-Hyd r oxy-2-m eth ylbu ta n e (8). Water (5
mL) and cerium ammonium nitrate (10% in weight compared
to the epoxide) were placed in a 10 mL Pyrex glass tube
equipped with a magnetic stirrer, and then 7 mmol of 2 was
added under rapid stirring. The glass tube was closed by a
screwed stopper with a joint of sealing covered with Teflon,
and stirring was maintained for about 2 h. The aqueous layer
was saturated with NaCl, and the diol was extracted with
ether. The organic layer was dried (anhydrous Na2SO4) and
concentrated under vacuum to give the corresponding crude
diol, which was purified by using semipreparative HPLC
(column C18, eluent 60:40 methanol/water). Characterization
bottomed flask equipped with
a magnetic stirrer and a
dropping funnel. The reaction mixture was cooled at -5 °C by
using an ice bath, and 1.08 mmol of 2-chloroethylphosphonyl-
dichloride in 5 mL of benzene was added dropwise under
stirring for about 3 h. At the end of the addition, the stirring
was maintained for 2 h, and then the amine chlorohydrate was
separated from the solution by centrifugation. The liquid layer
was isolated, and then the benzene was evaporated in a
vacuum with a rotating evaporator, yield 95%.
Ch a r a cter iza tion of 2-(2-Ch lor oeth yl)-4,4,5-tr im eth yl-
2-oxo-1,3,2-d ioxa p h osp h ola n e (5) (F igu r e 3). Diastereomer
3
5a (R,S or S,R): 1H NMR (CDCl3) δ 1.33 [dt; CH3(a); J HH
)
1
3
of 8: H NMR (CDCl3) δ 1.08 [d; CH3 in R of CH(OH); J HH
)
6.9 Hz], 1.31 [s; CH3(b)], 1.55 [s; CH3(c)], 2.45 (dt; CH2P; 3J HH
6.3 Hz], 1.10 and 1.30 [2 s; CH3 in R of C(OH)], 3.55 [q; tertiary
H of CH(OH)]; 13C NMR (CDCl3) δ 17.7 [s; CH3 in R of
CH(OH)], 22.75 and 26.61 [s; CH3 in R of C(OH)], 73.42 [s;
C(OH)], 74.36 [s, CH(OH)].
2
3
) 7.9 Hz; J HP ) 18.2 Hz), 3.75 (dt; ClCH2; J HH ) 7.9 Hz;
3
3
2J HP ) 12.2 Hz), 4.54 (dq; CH-O-P; J HH ) 6.4 Hz; J HP
)
2.1 Hz); 13C NMR (CDCl3) δ 15.47 [s; CH3(a)], 22.05 [s;
CH3(b)], 26.31 [d; CH3(c); 3J HP ) 5.7 Hz], 32.01 (d; CH2P; 1J PC
) 128.7 Hz), 37.62 (s; ClCH2), 82.01 (s; CH-O-P), 85.10 (s,
COP); 31P NMR (CDCl3) δ 39.3. Diastereomer 5b (R,R or
S,S): 1H NMR (CDCl3) δ 1.39 [d; CH3(a); 3J HH ) 6.4 Hz], 1.42
NMR Ch a r a cter iza tics of th e Der iva tives 6 a n d 7.9
3-Methylbutan-2-one(6): 1H NMR (CDCl3) δ 1.10 (d; CH3 in R
of CH), 2.15 (s; CH3 in R of CdO), 2.60 (m; CH); 13C NMR
(CDCl3) δ 17.5 (s; CH3 in R of CH), 26.8 (s; CH3 in R of CdO),
40.9 (s; CH), 211.5 (s; CdO). 3-Methyl-3-buten-2-ol (7): 1H
NMR (CDCl3) δ 1.20 [d; CH3 in R of CH(OH)], 1.75 (s; CH3 on
CdC), 4.20 [m; tertiary H of CH(OH)], 4.80-4.95 (d; CdCH2);
13C NMR (CDCl3) δ 18 (s; CH3 on CdC), 22 [s; CH3 in R of
CH(OH)], 65 [s; CH(OH)], 115 (s; -C(CH3)d), 145 (s; dCH2).
3
[s; CH3(b)], 1.48 [s; CH3(c)], 2.45 (dt; CH2P; J HH ) 7.9 Hz;
2J HP ) 18.2 Hz), 3.80 (dt; ClCH2; J HH ) 7.9 Hz; J HP ) 11.3
3
2
Hz), 4.32 (dq; CH-O-P; J HH ) 6.4 Hz; J HP ) 1.9 Hz); 13C
3
3
3
NMR (CDCl3) δ 15.62 [s; CH3(a); J HP ) 8.5 Hz], 25.95 [d;
CH3(b); 3J HH ) 8.4 Hz], 22.00 [s; CH3(c)], 30.90 (d; CH2P; 1J PC
) 135.04 Hz), 37.49 (s; ClCH2), 83.82 (s; CH-O-P), 86.70 (s,
COP); 31P NMR (CDCl3) δ 39.1.
J O001453P