Chiral P-heterocycles: Efficient method for the resolution of 3-methyl-3-phospholene 1-oxides

Article abstract of DOI:10.1080/10426500701764890

The enantiomers of 1-aryl-, 1-alkyl- and 1-alkoxy-3-methyl-3-phospholene 1-oxides were separated in good yields and in high enantiomeric excesses (up to >99% ee) by resolution via formation of diastereomeric complexes with (-)-(4R,5R)-4,5-bis(diphenylhydr

Full text of DOI:10.1080/10426500701764890

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Phosphorus, Sulfur, and Silicon
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Chiral P-Heterocycles: Efficient
Method for the Resolution of 3-
Methyl-3-phospholene 1-Oxides
Tibor Novak a , József Schindler a , Viktória Ujj
b , Mátyás Czugler c , Elemér Fogassy b & György
Keglevich b
a Research Group of the Hungarian Academy of
Sciences at the Department of Organic Chemical
Technology , Budapest University of Technology and
Economics , Budapest, Hungary
b Department of Organic Chemical Technology ,
Budapest University of Technology and Economics ,
Budapest, Hungary
c Hungarian Academy of Sciences, Chemical
Research Center , Budapest, Hungary
Published online: 21 Jun 2008.
To cite this article: Tibor Novak , József Schindler , Viktória Ujj , Mátyás Czugler ,
Elemér Fogassy & György Keglevich (2008) Chiral P-Heterocycles: Efficient Method for
the Resolution of 3-Methyl-3-phospholene 1-Oxides, Phosphorus, Sulfur, and Silicon
and the Related Elements, 183:2-3, 543-546, DOI: 10.1080/10426500701764890
To link to this article: http://dx.doi.org/10.1080/10426500701764890
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Phosphorus, Sulfur, and Silicon, 183:543–546, 2008
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500701764890
Chiral P-Heterocycles: Efficient Method for the
Resolution of 3-Methyl-3-phospholene 1-Oxides
1
1
2
´
´
Tibor Novak, Jozsef Schindler, Viktoria Ujj,
3
2
´
´
´
Matyas Czugler, Elemer Fogassy,
2
¨
and Gyorgy Keglevich
1Research Group of the Hungarian Academy of Sciences at the
Department of Organic Chemical Technology, Budapest University of
Technology and Economics, Budapest, Hungary
2Department of Organic Chemical Technology, Budapest University of
Technology and Economics, Budapest, Hungary
3Hungarian Academy of Sciences, Chemical Research Center, Budapest,
Hungary
The enantiomers of 1-aryl-, 1-alkyl- and 1-alkoxy-3-methyl-3-phospholene 1-oxides
were separated in good yields and in high enantiomeric excesses (up to >99%
ee) by resolution via formation of diastereomeric complexes with (–)-(4R,5R)-
4,5-bis(diphenylhydroxymethyl)-2,2-dimethyldioxolane (TADDOL) or (–)-(2R,3R)-
α,α,αꢀ,αꢀ-tetraphenyl-1,4-dioxaspiro[4.5]decan-2,3-dimethanol.
Keywords Chiral P-heterocycles; diastereomeric complex formation; resolution;
TADDOL
INTRODUCTION
Phosphine oxides form an important class of phosphorus compounds,
since they are precursors of the corresponding phosphines which,
in turn, may serve as ligands in transition metal complexes that
can be applied in several highly efficient homogenous catalytic
processes.1,2 Five-membered P-heterocycles, such as 1-substituted-3-
phospholene 1-oxides (e.g., 1) are of synthetic importance, as they
can be used as starting materials in the preparation of a variety
The authors are grateful for the financial support from the Hungarian Scientific Re-
search Fund (OTKA, Grants No. T 067679 and T 042725). TN is a recipient of a Bolyai
fellowship.
Address correspondence to Gyo¨rgy Keglevich, Department of Organic Chemistry and
Technology, Budapest University of Technology and Economics, H-1521 Budapest, Hun-
gary. E-mail:keglevich@mail.bme.hu
543

544
T. Novak et al.
FIGURE 1 Racemic phospholene oxides (1) and the resolving agents (2 and
3).
of five-, six-, seven-, and eight-membered P-heterocycles including
bridged derivatives.3–6 Pietrusiewicz and coworkers reported sev-
eral methods for the preparation of optically pure 1-phenyl-2- or 1-
phenyl-3-phospholene 1-oxides and their epoxide derivatives based
on dipolar cycloaddition,7enantioselective desymmetrization,8–10 and
quaternerization of their deoxigenated derivatives with a chiral
reactant.10A simple procedure for the resolution of 1-substituted-3-
methyl-3-phospholene 1-oxides (1) by separation of the diastereomeric
complexes formed by the interaction of (R)-1 or (S)-1 with chiral hosts,
such as TADDOL 2 or TADDOL analogue 311 is described (Figure 1).12
Racemic 1-substituted-3-methyl-3-phospholene 1-oxides (1) were re-
solved by adding half equivalent of (–)-TADDOL (2) or its derivatives (3)
to their hot ethyl acetate solution and precipitating an 1:1 crystalline
complexes (+ or −)-1·(–)-2 by the addition of hexane. After two recrystal-
lizations from a mixture of ethyl acetate–hexane and flash chromatog-
raphy on a silica gel, complexes (+ or −)-1a–h were regenerated and
analyzed on a chiral HPLC column (Chiralpack AD) or on a chiral GC
column (BETA DECTM). The optical purities of (+ or −)-1a–h are shown
in Table I. As it can be seen, in all cases resolution took place and quite
often we could separate the optically pure compound.
The complete resolution procedure is shown for 1a with TADDOL 2
in Figure 2.
TABLE I Optical Purities of P-Heterocycles (1a–h) After Resolution
with 2 or 3
Optical purity of the products [ee %]
Resolving agent
1a
1b
1c
1d
1e
1f
1g
1h
2
3
97
>99
57
>99
69
>99
70
>99
24
58
95
44
95
>99
>99
89∗
∗for the 1:2 complex formed by the use of one equivalent of 3.

Chiral P-Heterocycles
545
O
O
+
Ph
Ph
Ph
Ph
P
O
Ph
OH HO
(-)-2
( )-1a
0.5 eq.
EtOAc/hexane
(-)-1a·(-)-2 ↓
71% de (72%)
EtOAc/hexane
(+)-1a
mother liquor
36% ee (70%)
(-)-1a·(-)-2 ↓
88% de (54%)
EtOAc/hexane
O
O
Ph
Ph
Ph
(+)-2
Ph
OH HO
0.68 eq.
EtOAc/hexane
mother liquor
(-)-1a·(-)-2 ↓
97% de (44%)
column chrom.
(+)-1a·(+)-2 ↓
EtOAc/hexane
mother liquor
P
column
chrom.
O
Ph
mother liquor
(+)-1a·(+)-2 ↓
99% de (28%)
P
(-)-1a
97% ee (43%)
O
Ph
(+)-1a
99% ee (25%)
FIGURE 2 The complete resolution procedure of 1a with TADDOL 2.
To clarify the absolute configuration of 1a, 1e, and 1f, (−)-1a·(−)-
2·acetone, (+)-1e·(−)-3 and (+)-1f·(−)-2 were subjected to single crystal
X-ray analysis. The absolute configuration of (−)-1a, (+)-1e, and (+)-1f,
was found to be S, R, and R, respectively. X-ray structure showed inter-
and intramolecular H-bridges which held the supramolecular formation
together. These short contacts are shown for the case of (−)-1a·(−)-
2·acetone on Figure 3.
FIGURE 3 Inter- and intramolecular H-bridges in the crystall structure of
(–)-1a·(–)-2·acetone.

546
T. Novak et al.
The resolution procedure described above is the first example for
the resolution of a cyclic phosphine oxide or a phosphinate via in-
clusion complex formation. The method comprises crystallization with
TADDOL 2 or its analogue 3, recrystallization of the supramolecular
formation and the regeneration of 1. Our procedure form a simple and
convenient method for the preparation of both enantiomers with high
enantiomeric purity. The method introduced may be suitable for the
resolution of other P-heterocycles or acyclic P-compounds with P
function, as well.
O
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