A practical and efficient method for the resolution of 3-phospholene 1-oxides via coordination complex formation

Article abstract of DOI:10.1002/chir.20821

A simple, efficient, and economical method based on the combination of the exceptional behavior of o,o′-dibenzoyl- or o,o′-di-p-toluyl-(2R,3R)- tartaric acid in chiral recognition processes, and the coordination ability of calcium or magnesium ion was developed for the resolution of phospholene oxides 1. The calcium or magnesium salt of (2)-o,o′-dibenzoyl-(2R,3R)-tartaric acid 2,4-6 or calcium hydrogen (2)-o,o′-di-ptoluyl-( 2R,3R)-tartrate 3 may form crystalline diastereomeric coordination complexes with the appropriate antipode of substituted 3-phospholene oxides 1 that makes possible efficient resolutions. Optically active phospholene oxides 1 were prepared directly by simply crystallization and digestion of the corresponding diastereomeric complexes so formed. Thermal behavior of the crystalline diastereomeric complexes was studied by simultaneous TG/DTA. The novel method may be of more general value in respect of the resolution of tertiary phosphine oxides.

Full text of DOI:10.1002/chir.20821

CHIRALITY 22:699–705 (2010)
A Practical and Efficient Method for the Resolution of
3-Phospholene 1-oxides via Coordination Complex Formation1
1,2
1
2
3
1
1
´
´
´
´
´
´
¨
VIKTORIA UJJ, PETER BAGI, JOZSEF SCHINDLER, JANOS MADARASZ, ELEMER FOGASSY, AND GYORGY KEGLEVICH
1Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, H-1521 Budapest, Hungary
2Research Group of the Hungarian Academy of Sciences at the Department of Organic Chemistry and Technology,
Budapest University of Technology and Economics, H-1521 Budapest, Hungary
3Department of Inorganic and Analytical Chemistry, Budapest University of Technology and Economics, H-1521 Budapest, Hungary
ABSTRACT
A simple, efficient, and economical method based on the combination
of the exceptional behavior of o,o0-dibenzoyl- or o,o0-di-p-toluyl-(2R,3R)-tartaric acid in
chiral recognition processes, and the coordination ability of calcium or magnesium ion
was developed for the resolution of phospholene oxides 1. The calcium or magnesium
salt of (2)-o,o0-dibenzoyl-(2R,3R)-tartaric acid 2,4-6 or calcium hydrogen (2)-o,o0-di-p-
toluyl-(2R,3R)-tartrate 3 may form crystalline diastereomeric coordination complexes
with the appropriate antipode of substituted 3-phospholene oxides 1 that makes possible
efficient resolutions. Optically active phospholene oxides 1 were prepared directly by
simply crystallization and digestion of the corresponding diastereomeric complexes so
formed. Thermal behavior of the crystalline diastereomeric complexes was studied by si-
multaneous TG/DTA. The novel method may be of more general value in respect of the
C
VV
resolution of tertiary phosphine oxides. Chirality 22:699–705, 2010.
2010 Wiley-Liss, Inc.
KEY WORDS: coordinative resolution; P-chiral phospholene oxides; tartaric acid
derivatives; solvent dependence
INTRODUCTION
bonds between the racemic bases and TA or its derivatives
is established readily and quantitatively.8–10 Dibenzoyltar-
taric acid can also be used in silver salt formation for the
resolution of phosphonium salts via diastereomeric salt
formations.11,12 Dibenzoyl-(2R,3R)-tartaric acid (DBTA)
and di-p-toluyl-(2R,3R)-tartaric acid (DPTTA) can be used
for the resolution of racemates without basic character, as
they can result supramolecular formations with several
chiral alcohols.7,13 Noyori and coworkers14 described the
synthesis of optically active BINAP via resolution of its P-
oxide with DBTA. The method has been used successfully
for separation of the optical isomers of a number of
bis(phosphine) oxides.7 Combination of the exceptional
behavior of DBTA in chiral recognition processes and the
coordination ability of Ca21, Zn21, or Cu21 was also
applied in enantiomeric separations,7 such as in the resolu-
tion of a-hydroxy-esters15,16 and a-alkoxy-carboxylic
acids16 and in the enantiomeric enrichment of alcohols
and a-alkoxyalkohols.17
In the last few years, our attention was focused on the
preparation of chiral phosphines; since this area is a cur-
rent challenge in synthetic organic chemistry because
their transition metal complexes may provide high enantio-
selectivity in homogenous catalytic reactions.2,3 From
practical point of view, the preparation and resolution of ra-
cemic phosphine oxides followed by deoxygenation of the
separated enantiomers is more appropriate than enantiose-
lective synthesis.
Resolution of racemates via diastereomeric intermedi-
ates is the most frequently used method for the production
of new compounds in enantiomerically pure form, applica-
ble also on the industrial scale.4,5 Depending on the type
of interaction formed between the resolving agent and the
enantiomer, the resolutions can be achieved via diastereo-
meric salts (involving ionic bonds), diastereomeric com-
pounds (involving covalent bonds), diastereomeric coordi-
nation complexes (involving dative bonds), and diastereo-
meric molecular complexes (involving secondary
interactions). Certainly, the resolving machinery is
affected by weaker secondary interactions in all cases.6,7
Natural (2R,3R)-tartaric acid (TA) and its derivatives
play an important role as resolving agents in the prepara-
tion of single enantiomers. The efficiency of TA derivatives
in a wide range of chiral recognition processes is the con-
sequence of the C2 symmetry and relatively large number
of functional groups of these molecules.7 The resolution of
racemic bases can be accomplished by diastereomeric salt
Other methods were also described in the literature for
the preparation of optically active P-compounds. These
approaches, however, proved to be useful only in special
cases.12
Contract grant sponsor: Hungarian Scientific Research Fund (OTKA);
Contract grant numbers: T075236, T067679.
*Correspondence to: Eleme´r Fogassy, Budafoki u´ t 8., Budapest H-1521,
Hungary. E-mail: efogassy@mail.bme.hu
Received for publication 20 May 2009; Accepted 28 October 2009
DOI: 10.1002/chir.20821
Published online 8 February 2010 in Wiley InterScience
formation with TA derivatives. The formation of ionic (www.interscience.wiley.com).
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VV
2010 Wiley-Liss, Inc.

700
UJJ ET AL.
Scheme 1. The phospholene oxides 1 and the resolving agents (2)-2 and (2)-3.
The exceptional behavior of TA derivatives prompted us
The 3-phospholene 1-oxides 1a-h were synthesized as
to use them in the resolution of phospholene oxides 1. described earlier.20,22–25 (2)-o,o0-Dibenzoyl-(2R,3R)-tartaric
Recently, we have described that substituted 3-phospho- acid and (2)-o,o0-di-p-toluyl-(2R,3R)-tartaric acid were pur-
lene 1-oxides 1 can be resolved via molecular complex for- chased from Aldrich Chemical Co.
mation with (2)-(4R,5R)-4,5-bis(diphenylhydroxymethyl)-
2,2-dimethyldioxolane (TADDOL)18 or its spiro derivative,
(2)-(2R,3R)-a,a,a0,a0-tetraphenyl-1,4-dioxaspiro[4.5]decan-
Resolution of 1-Propyl-3-methyl-3-phospholene 1-oxide
2,3-dimethanol.19–21 In contrast, TA and its o,o0-dibenzoyl-
(DBTA) or o,o0-di-p-toluyl- (DPTTA) derivatives did not
form molecular complex with phospholene oxides 1. How-
ever, we have found that using calcium hydrogen (2)-o,o0-
dibenzoyl-(2R,3R)-tartrate [(2)-Ca(H-DBTA)2, (2)-2] or
calcium hydrogen (2)-o,o0-di-p-toluyl-(2R,3R)-tartrate [(2)-
Ca(H-DPTTA)2, (2)-3], 1-aryl-3-phospholene 1-oxides 1a
and 1b can be resolved via diastereomeric coordination
complex formation.1 This method is based on the coordi-
nation ability of Ca21 ion toward the oxygen atom of the
P¼¼O moiety.1 In addition, the o,o0-dibenzoyltartrate or o,o0-
di-p-toluyltartrate units play an important role in the forma-
tion of complexes that crystallize well.7 In this article, we
study if this novel resolution method can be extended to
any 3-phospholene oxides having, for example, 1-aryl-, 1-
alkyl-, or 1-alkoxy substituents (Scheme 1).
1f with Calcium hydrogen o,o0-dibenzoyl-(2 R,3 R)-
tartrate (2)-2ÐRepresentative Procedure A
To 0.46 g (0.61 mmol) of (2)-2 in 1.6 ml of a 10:1 mix-
ture of ethanol–water was added 0.20 g (1.23 mmol) of rac-
1f. After the addition, colorless crystals appeared immedi-
ately. After standing at room temperature for 4 h, the crys-
tals were filtered off to give 0.41 g (74%) of Ca[((S)-1f)(H-
DBTA)2(H2O)] with a de of 37%. The complex was taken
up in 1.6 ml of a 10:1 mixture of ethanol–water and the
suspension was stirred at 608C for 24 h. The crystals were
filtered off to give 0.23
g (42%) of Ca[((S)-1f)(H-
DBTA)2(H2O)] with a de of 78% as colorless crystals. The
digestion was repeated and 0.10 g (18%) of Ca[((S)-1f)(H-
DBTA)2(H2O)] with a de of 96% was obtained (mp. 1528C,
dec.). The phospholene oxide (S)-1f was recovered by
treatment of the chloroform solution (2 ml) of the complex
with 2 ml of a 10% aqueous ammonia. The organic phase
was washed with 0.5 ml of water, dried (Na2SO4), and con-
centrated to give 17 mg (0.11 mmol, 17%) of (S)-1-propyl-3-
MATERIALS AND METHODS
The ratio of ligands in the diastereomeric complexes methyl-3-phospholene 1-oxide (S)-1f with an ee of 96%;
1
1
were determined by H NMR. The H NMR spectra were [a]25D 5 213.9 (c 0.6, CHCl3).
taken on a Bruker DRX-500 spectrometer operating at 500
The resolutions of 1-substituted-3-methyl-3-phospholene
MHz in DMSO. The enantiomeric excess (ee) values were 1-oxides 1a-h with resolving agents (2)-2 or (2)-3 were
determined by chiral HPLC (Chiralpack AD-H column 250 carried out according to the representative procedure A.
3 4.6 mm ID, Daicel Chem. Ind., using hexane/isopropa- The conditions and the results of the resolutions are
nol 85/15 as the eluent with a flow rate of 0.8 ml/min, T 5 shown in Tables 1 and 2. Retention times by chiral
208C, UV detector k 5 254 nm) or by chiral GC (was car- HPLC: 9.3 min for (R)-1a and 10.9 min for (S)-1a; 11.2
ried out on Agilent 4890D instrument equipped with a min for 1b, and 13.5 min for 1b; 11.5 min for (R)-1c and
BETA DEXTM 120 column, 30 m 3 0.25 mm, 0.25 lm film, 15.5 min for (S)-1c; 10.5 min for (R)-1d, and 12.7 min for
FID detector, nitrogen as carrier gas, injector 2408C, de- (S)-1d. Retention times by chiral GC (program for 1e-g: 2
tector 3008C, head pressure: 15 psi, at 1:100 split ratio). min at 1408C, 208C/min to 1908C, then kept at 1908C):
Optical rotations were determined on a Perkin-Elmer 241 12.1 min for (R)-1e and 12.3 min for (S)-1e; 13.9 min for
polarimeter. Simultaneous thermogravimetric (TG) and (R)-1f and 14.2 min for (S)-1f; 9.1 min for (S)-1g and 9.3
differential thermal analytical (DTA) measurements were min for (R)-1g. Retention times by chiral GC (program for
carried out on a STD 2960 Simultaneous DTA-TGA appara- 1h: 25 min at 1408C): 21.8 min for (S)-1h, 22.2 min for
tus (TA Instruments Inc., New Castle, DE).
(R)-1h.
Chirality DOI 10.1002/chir

RESOLUTION OF 3-PHOSPHOLENE 1-OXIDES
701
TABLE 1. Optimized conditions for the resolution of rac-3-phospholene 1-oxides 1 using 0.25 equiv. of resolving
agent (–)-2
Subst.
Coordination complexa
Solvents
Yieldb (%)
52
Eec (%)
96 (53)
Sd
Abs. config.e
Mpf (8C) Dec.
1a
Ca[(1a)2(H-DBTA)2(H2O)]
EtOAc-EtOH 1:1g [4]
EtOH-Water 10:1h [4]
EtOAc-EtOH 1:1g [4]
EtOH-Water 10:1h [4]
MeCN-EtOH 2:3g [5]
MeCN-EtOH 1:1h [4]
MeCN-EtOH 2:3g [5]
MeCN-EtOH 1:1h [4]
EtOH-Water 10:1g [3]
EtOH-Water 10:1h [3]
MeCN-EtOH 2:3g [5]
MeCN-EtOH 1:1h [4]
MeCN-EtOH 2:3g [5]
MeCN-EtOH 1:1h [4]
0.50
R
177
1b
1c
1d
1fi
1g
1h
Ca[(1b)2(H-DBTA)2]
Ca[(1c)2(H-DBTA)2]
Ca[(1d)2(H-DBTA)2]
Ca[(1f)(H-DBTA)2(H2O)]
Ca[(1g)2(H-DBTA)2]
Ca[(1h)2(H-DBTA)2]
42
33
28
18
29
36
99 (60)
93 (68)
44 (31)
96 (37)
91 (67)
92 (31)
0.42
0.31
0.12
0.17
0.26
0.33
177
166
151
152
164
171
R
S
S
R
S
aThe ratio of 1 and resolving agent (–)-2 was determined by 1H NMR. Amount of the bound water in the complexes was measured by simultaneous
TG/DTA method.
bBased on the half of the racemate 1 that is regarded to be 100% for each antipode.
cDetermined by chiral HPLC or chiral GC after digestion (and after crystallization).
dResolving capability, also known as the Fogassy parameter.26
eDetermined by X-ray analysis and CD spectroscopy.19,20
fThe melting was accompanied by decomposition of the diastereomeric complex.
gMixture of solvents for crystallization [ml of solvent/g of resolving agent (–)-2].
hMixture of solvents for digestion [ml of solvent/g of resolving agent (–)-2].
iResolution was achieved with 0.5 equiv of (–)-2.
Resolution of 1-Phenyl-3-methyl-3-phospholene 1-oxide
1a with Magnesium hydrogen o,o0-dibenzoyl-(2 R,3 R)-
tartrate (2)-5ÐRepresentative Procedure B
orless crystals (mp. 1698C, dec.). The phospholene oxide
(R)-1a was recovered by treatment of the chloroform solu-
tion (2 ml) of the complex with 2 ml of a 10% aqueous am-
monia. The organic phase was washed with 0.5 ml of
water, dried (Na2SO4), and concentrated to give 40 mg
(0.21 mmol, 27%) of (R)-1-phenyl-3-methyl-3-phospholene
1-oxide (R)-1a with an ee of 60%.
To 0.30 g (0.78 mmol) of (2)-DBTAꢀH2O and 16 mg
(0.39 mmol) of magnesium oxide in 1.0 ml of a 10:1 mix-
ture of ethanol–water was added to 0.30 g (1.57 mmol) of
rac-1a in 1.6 ml of ethyl acetate. After standing at room
temperature for 24 h, the crystals were filtered off to give
0.17 g (39%) of Mg[((R)-1a)2(H-DBTA)2] with a de of 50%.
The complex was taken up in 2.4 ml of a 3:5 mixture of
ethanol–ethyl acetate, and the suspension was stirred at
608C for 24 h. The crystals were filtered off to give 0.13 g
RESULTS AND DISCUSSION
Resolution of 3-Phospholene 1-oxides
Using (2)-Ca(H-DBTA)2
As an extension, our simple method utilizing (2)-Ca(H-
(30%) of Mg[((R)-1a)2(H-DBTA)2] with a de of 60% as col- DBTA)2 [(2)-2] or (2)-Ca(H-DPTTA)2 [(2)-3], which
TABLE 2. The resolution of rac-3-phospholene 1-oxides 1 using resolving agent (–)-3
Subst.
Coordination complexa
Yieldb (%)
Eec (%)
Sd
Abs. config.e
Mpf (8C) Dec.
1ag
1b
1c
1d
1e
1f
Ca[(1a)(H-DPTTA)2(H2O)]
Ca[(1b)2(H-DPTTA)2(H2O)]
Ca[(1c)2(H-DPTTA)2]
Ca[(1d)2(H-DPTTA)2]
Ca[(1e)2(H-DPTTA)2(H2O)2]
Ca[(1f)2(H-DPTTA)2]
55
29
13
15
34
42
44
93 (54)
69 (50)
45 (28)
32 (20)
73 (45)
41 (33)
75 (55)
Racemate
0.51
0.20
0.06
0.05
0.25
0.17
0.33
S
164
183
R
S
S
S
R
169
191
1g
1h
Ca[(1g)2(H-DPTTA)2]
Ca[(1h)2(H-DPTTA)2]
aThe ratio of 1 and resolving agent (–)-3 was determined by 1H NMR. Amount of the bound water in the complexes was measured by simultaneous
TG/DTA method.
bBased on the half of the racemate 1 that is regarded to be 100% for each antipode.
cDetermined by chiral HPLC or chiral GC after digestion (and after crystallization).
dResolving capability, also known as the Fogassy parameter.26
eDetermined by X-ray analysis and CD spectroscopy.19,20
fThe melting was accompanied by decomposition of the diastereomeric complex.
gResolution was achieved with 0.5 equiv of (–)-3.
Chirality DOI 10.1002/chir

702
UJJ ET AL.
Scheme 2. The general resolution process of rac-3-phospholene 1-oxides 1 using resolving agent (2)-2.
was successfully used for the resolution of 3-phospholene DBTA)2]was increased to 93, 44, 91, and 92%, respectively,
1-oxides 1a and 1b1 was further developed for the resolu- after the first digestion, and the complexes were obtained
tion of 1-aryl-, 1-alkyl-, and 1-alkoxy-3-phospholene 1-oxides in 33, 28, 29, and 36% yield, respectively.
1c-h (Scheme 2).
From practical point of view, the refined resolution pro-
According to our original procedure, to the solution of cess using (2)-2 seemed to be quite general and more ad-
(2)-Ca(H-DBTA)2 [(2)-2] in hot ethanol was added a so- vantageous as compared to that accomplished with TAD-
lution of 1-substituted phospholene oxide 1 in ethyl ace- DOL derivatives. Although, applying TADDOL derivatives
tate. After crystallization at room temperature, the precipi- for the resolution of phospholene oxides 1, pure enantiom-
tate was filtered off to give diastereomeric complex ers could be obtained, but it is a disadvantage that the
Ca[(1)2(H-DBTA)2] that was further purified by digestion resolving agent is considerably more expensive and
in a 10:1 mixture of ethanol and water at 608C. The phos- decomposition of the diastereomeric complexes requires
pholene oxides 1 were recovered by the treatment of the column chromatography. At the same time, our new proce-
chloroform solution of the complexes Ca[(1)2(H-DBTA)2] dure applies a low-cost resolving agent, and the method
with a 10% aqueous ammonia. The enantiomeric excess can be carried out easily on a bigger scale, moreover, the
(ee) of products was determined by chiral HPLC (for 1c decomposition of diastereomeric complexes is very sim-
and 1d), or by chiral GC (for 1e-h). The resolution pro- ple. On the other hand, the calcium salt of o,o0-dibenzoyl-
cess by our original method using agent (2)-2 in the case (2R,3R)-tartaric acid (2)-2 shows good compatibility with
of 1-(2-methylphenyl)- and 1-(4-methylphenyl)-3-phospho- phospholene oxides 1.
lene 1-oxides 1c and 1d was completely inefficient, as the
products were racemic after the first precipitation. The re-
solution by our original method of alkyl- and alkoxy-phos-
A Detailed Study on the Resolution of 1-Propyl-3-methyl-
3-phospholene 1-oxide Using (2)-Ca(H-DBTA)2
pholene oxides 1e-h led to poor results. After the diges-
tion and decomposition, phospholene oxides 1e-h were the mixture of ethanol and ethyl acetate, the R enantiomer
obtained with an ee of 49, 61, 75, 32%, respectively. of 1f was enriched in the complex Ca[(1f)2(H-DBTA)2]
In the course of the crystallization of 1f with (2)-2 in
As it can be seen, the original process elaborated for the with an ee of 7%, but, surprisingly, after the digestion in
resolution of 1a and 1b with (2)-2 could not be adapted aqueous ethanol, the other, (S) enantiomer was enriched
efficiently for the resolution of 1c-h. Refining the condi- in the complex Ca[(1f)(H-DBTA)2] with an ee of 61%, and
tions of the resolution, such as choosing more appropriate the ratio of the ligands was also changed. The nature of
solvents, varying the amount of solvents, and the amount solvents used, effected the enantiocomplementarity.
of resolving agent, we could significantly increase the effi- Hence, the configuration of the incorporated phospholene
ciency of the resolutions. Results of the optimized resolu- oxide 1f in the diastereomeric complexes depends on the
tions of 1a-h using (2)-2 are shown in Table 1.
solvents applied for crystallization. Therefore, resolution of
In all cases but one, the stoichiometry of the precipi- 1f using (2)-2 was achieved in different mixtures of sol-
tated complexes was the same corresponding to structure vents. The best result (78% ee) for the preparation of (S)-
Ca[(1)2(H-DBTA)2], therefore, the resolutions were 1f was obtained, when the solvent was aqueous ethanol.
achieved by the use of 0.25 equivalent of the resolving The resolution machinery is affected by the presence of
agent (2)-2. In the course of the resolution of 1f using water, and it must be regarded as a kind of reactant. For
(2)-2, the Ca[((S)-1f)(H-DBTA)2(H2O)]complex was the preparation of (R)-1f with an ee of 39%, a 1:1 mixture
formed in aqueous ethanol, so 0.5 equiv. of (2)-2 was of acetone and ethanol should be used.
used.
As a result of the opposite antipode preference of (2)-2
It was found that changing ethyl acetate–ethanol to ace- in respect of different mixture of solvents used (as shown
tonitrile–ethanol in the resolution of aryl- and alkoxy-sub- above), we could separate both enantiomers of 1f using
stituted derivatives 1c-d, g-h, the ee in most cases, natural TA derived resolving agent (2)-2. The resolution
increased above 90%. When acetonitrile–ethanol was used, process of phospholene oxide 1f is shown in Scheme 3.
the de of Ca[((R)-1c)2(H-DBTA)2], Ca[((S)-1d)2(H- After the crystallization and the first digestion in a 10:1
DBTA)2], Ca[((R)-1g)2(H-DBTA)2], and Ca[((S)-1h)2(H- mixture of ethanol and water, complex Ca[((S)-1f)(H-
Chirality DOI 10.1002/chir

RESOLUTION OF 3-PHOSPHOLENE 1-OXIDES
703
Scheme 3. The resolution process for 1-propyl-3-methyl-3-phospholene 1-oxide 1f using resolving agent (2)-2. (A: digestion; B: NH3/H2O; C: extrac-
tion, evaporation; D: evaporation).
Resolution of 3-Phospholene 1-oxides
DBTA)2(H2O)] (mp: 1528C, dec.) with a de of 87% and in a
33% yield was obtained. To get the other antipode of 1f,
the mother liquor of the crystallization and the filtrate of
the digestion were combined and the mixture so obtained
was treated with aqueous ammonia to afford the (R)-1f
with an ee of 23% and in a 95% yield. The enantiomeric
mixture was further purified using 0.61 equiv. of (2)-2
(0.5 equiv. for (R)-1f) in a mixture of ethanol and acetone.
After crystallization and digestion, complex Ca[((R)-
1f)2(H-DBTA)2] (mp: 1668C, dec.) with a de of 57% was
obtained in a yield of 38%.
Using (2)-Ca(DBTA)
So far, in all experiments the ratio of CaO and DBTA or
DPTTA was 1:2, and an acidic calcium salt was prepared.
To get a neutral calcium salt (Scheme 5), 1:1 ratio of CaO
and DBTA was used for the resolution of 1a and 1c. The
resolution of 1a and 1c proved to be efficient as Ca[((R)-
1a)(DBTA)] and Ca[((R)-1c)(DBTA)] were obtained with
a de of 90 and 71% in a yield of 18 and 22%, respectively, af-
ter crystallization and digestion from a mixture of ethyl ac-
etate and aqueous ethanol. In the case of 1b,d,e-h the re-
solution process was less efficient, as the de of Ca[(1)(DB-
TA)]was lower than 50% and it was obtained in a low yield.
Resolution of 3-Phospholene 1-oxides
Using (2)-Ca(H-DPTTA)2
Resolution of 3-Phospholene 1-oxides
Using (2)-Mg(H-DBTA)2 and (2)-Mg(DBTA)
The resolution of phospholene oxides 1c-g was also
achieved with resolving agent (2)-3 as shown in Scheme
Theoretically, any metal ion can be used as the central
4 and Table 2. The crystallization and digestion of com- ion of the coordination compounds.7 To expand the range
plexes were accomplished in a 10:1 mixture of ethanol and of such coordination resolutions, the central metal ion was
water. In general, the resolution of phospholene oxides 1 replaced. When ZnO, Cu(OAc)2, Co(OAc)2 were used in
using (2)-3 proved to be less efficient as compared to the place of CaO, none of them could form complexes with
resolutions accomplished with (2)-2. However, for the re- phospholene oxides 1, but using MgO, colorless crystals
solution of ethyl- and ethoxy-substituted derivatives 1e were obtained, and an enantiomeric discrimination was
and 1g, respectively, resolving agent (2)-3 was found to observed. The resolution of 1a and 1f was accomplished
be more appropriate considering the resolving capabilities. according to the representative procedure B using a 1:2
Scheme 4. The general resolution process of rac-3-phospholene 1-oxides 1 using resolving agent (2)-3.
Chirality DOI 10.1002/chir

704
UJJ ET AL.
tained strongly bound water that is probably coordinated
water. Complexes are shown in Table 1 and 2.
CONCLUSION
A simple and economical procedure was developed for
the resolution of a variety of 3-methyl-3-phospholene 1-
oxides, such as 1-aryl-, 1-alkyl-, and 1-alkoxy-derivatives
1a-h via coordination complex formation using (2)-Ca(H-
DBTA)2 [(2)-2] and (2)-Ca(H-DPTTA)2 [(2)-3]. The
appropriate choice of the resolving agent and the optimum
conditions suitable for the efficient resolution of the given
phospholene oxide were explored for each particular case.
From among the eight 3-phospholene 1-oxides (1a-h)
studied, six species (1a-c,f-h) could be resolved with ee of
>90%. As a result of the opposite antipode preference of
(2)-2 in respect of different mixture of solvents used, we
could separate both enantiomers of 1f using the natural
tartaric acid derived resolving agent (2)-2. The new
method involving crystallization with (2)-2 or (2)-3 and
digestion of the corresponding diastereomeric complexes
may be of more general value and may be suitable for the
resolution of other tertiary phosphine oxides as well. As a
further extension and generalization, the resolution of 1
with (2)-Ca(DBTA) [(2)-4] or (2)-Mg(H-DBTA)2 [(2)-
5] was also accomplished. A detailed study with these
resolving agents is in progress. Simultaneous TG/DTA
investigations on samples of diastereomeric coordination
complexes provided information on their composition,
melting behavior and stability.
Scheme 5. The resolving agents (2)-4, (2)-5, and (2)-6.
ratio of MgO and DBTA, that is (2)-Mg(H-DBTA)2 [(2)-
5] (Scheme 5). The best result was obtained for the reso-
lution of 1a in a mixture of aqueous ethanol and ethyl ace-
tate to afford Mg[((R)-1a)2(H-DBTA)2] with a de of 60%
and in a 30% yield after digestion. In the case of the resolu-
tion of 1f, from a mixture of aqueous ethanol and diethyl
ether, complex Mg[((R)-1f)2(H-DBTA)2] was obtained
with a de of 64% and in a 35% yield. The presence of water
in the mixtures also had a significant importance to pro-
mote crystallization of the diastereomeric complexes. In
the case of 1b-e,g-h the resolution process was less effi-
cient, as the de of Mg[(1)(H-DBTA)] was lower than 50%
and it was obtained in a low yield.
The resolution of 1 was also attempted by using a 1:1 ra-
tio of MgO and DBTA that is (2)-Mg(DBTA) [(2)-6], but
this resolving agent could not form complexes with phos-
pholene oxides 1.
Thermoanalytical Investigations of the
Coordination Complexes
The simultaneous thermogravimetry and differential
thermoanalysis (TG/DTA) of the coordination complexes
have also provided valuable data on their composition,
melting behavior, and stability. The melting points of the
diastereomeric complexes are shown in Table 1 and 2. In
all cases, the diastereomeric coordination complexes of
the samples were found to be thermally stable up to their
melting, which occurred as sharp endothermic DTA-peaks
in the temperature range of 150–1958C. The complexes
melted with decomposition showing immediate weight
loss, and in most cases immediately after the appearance
of the endothermic peak of melting, an overlapping exo-
thermic peak could be seen as a result of decarboxyl-
ation27 of the calcium hydrogen dibenzoyl- or di-p-toluyl-
tartrates. The initial evolution of CO2 has been proven by
in situ evolved gas analysis measurements (TG/DTA-
EGA-MS).
Most of the samples released water in one or two steps
before melting and decomposition. We assumed that the
water leaving at lower than 908C was a weakly bound lat-
tice solvent of crystallization. On the other hand, the
bound water lost above 1008C was able to establish stron-
ger hydrogen bonds with the DBTA or DPTTA or more
probably they were coordinated to the central calcium ion
in the complexes. This latter significant interaction (coor-
dination) could influence the resolution mechanism, the
enantiomeric discrimination, and hence the preferred con-
figuration of the P-ligand and finally the stoichiometry of
the P-heterocycle in the diastereomeric coordination com-
plexes. On the basis of simultaneous TG and DTA exami-
nations, five diastereomeric coordination complexes con-
Chirality DOI 10.1002/chir
ACKNOWLEDGMENTS
The authors are grateful to Dr. Tibor Nova´k for the
fruitful discussions.
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