Efficient Method for the Resolution of 3-Methyl-3-phospholene 1-Oxides
Viktória Ujj
Department of Organic Chemistry and Technology
Budapest University of Technology and Economics
H-1521 Budapest, Hungary
Supervisors: Dr. Elemér Fogassy
Dr. György Keglevich
Dr. Tibor Novák
József Schindler
Chiral phosphine oxides are of synthetic importance, since they are precursors of the
corresponding phosphines which, in turn, may serve as ligands in transition metal complexes
that can be applied as catalysts in several highly efficient catalytic processes.1,2 Since P-chiral
organophosphorus compounds cannot be found in enantiomeric forms in the natural pool of
chirality,3 the primary source of such compounds is resolution and in some limited cases
asymmetric synthesis.1 Several methods described in the literature on the resolution of
phosphorus compounds are based on the formation of separable diastereomeric salts,
diastereomeric transition metal complexes and molecular complexes.1
A practical procedure for the enantiomeric resolution of 1-substituted-3-methyl-3phospholene 1-oxides 1 by separation of the diastereomeric associates (1·2 and 1·3) formed
by 1 with chiral hosts, such as TADDOL 2 or TADDOL analogue 3 are discussed.3,4 Racemic
1-substituted-phospholene oxides 1 were resolved by crystallization with half equivalent of
TADDOL 2 or TADDOL analogue 3 from the mixture of ethyl acetate and hexane. The 1:1
molecular complexes so obtained were recrystallized twice to give 1·2 and 1·3 in good optical
purities and in good yields. After flash chromatography on a silica gel, 3-methyl-3phospholene 1-oxides 1 were recovered in quantitative yield without the loss of chirality.
Complexes 1·2, 1·3 and the pure enantiomers of 1 were analyzed by chiral HPLC or chiral
GC. To clarify the absolute configuration of the complexes (1a·2, 1e·3, 1f·2) were subjected
to single crystal X-ray analysis.
O
Ph
P
O
O
Y
Ph
1
OH HO
O
Ph
Ph
Ph
Ph
O
Ph
OH HO
2
Ph
3
Y = alkyl, alkoxy, aryl
Y
enantiomeric
excess
Ph (a)
o-Me-Ph (b)
p-Me-Ph (c)
Naph (d)
Et (e)
Pr (f)
EtO (g)
>99
>99
>99
>99
60
95
95
We have developed a resolution procedure that is the first example of the enantiomeric
separation of a cyclic phosphine oxide or a phosphinate via inclusion complex formation. The
crystallization with TADDOL 2 or TADDOL analogue 3, the recrystallization of the complex
and the regeneration of 1 form a simple and convenient method for the preparation of both
enantiomers with high enantiomeric purity. The novel procedure seems to be of general value,
as can be applied for the resolution of chiral phosphine oxides and phosphinates.
References
1. Pietrusiewicz, K. M.; Zabłocka, M. Chem. Rev. 1994, 93, 1375-1411.
2. Noyori, R. Asymmetric Catalysis in Organic Synthesis, John Wiley & Sons, New York,
1994.
3. Novák, T.; Schindler, J.; Ujj, V.; Czugler, M.; Fogassy, E.; Keglevich, Gy. Tetrahedron:
Asymmetry 2006, 17, 2599-2602.
4. Ujj, V.; Schindler, J.; Novák, T.; Czugler, M.; Fogassy, E.; Keglevich, Gy. unpublished
results.