2
,3-bis(methylsulfonate) was used as the anchoring auxiliary in
right in the beginning of the synthetic pathway in order to avoid
separation of racemates later in the synthesis. The resulting
ligands exhibit good enantioselectivities with mostly quantita-
tive conversion of the substrates when used in asymmetric
hydrogenation reactions. This makes them a promising class of
ligands.
the desymmetrisation procedure, as this results in a C
2
-
6
symmetric ligand backbone. For hydrogenation experiments, 5
was used as a mixture of the two diastereomers. The difference
between them is the orientation of the methyl group introduced
with the chiral auxiliary towards the phosphorus lone pair. For
detailed studies on its influence on the ligand’s catalytic
behaviour separation of the diastereomers would be neces-
sary.
This work was supported by Bayer AG.
Hydrogenation experiments were performed under a hydro-
gen pressure of 3 bar at room temperature over a period of 24
hours using a variety of substrates. In Table 1, entries 1, 2 and
Notes and references
†
3
0.081 ml (0.127 g, 0.929 mmol) PCl dissolved in 30 ml toluene were
cooled to 278 °C before 0.53 ml (0.384 g, 3.79 mmol) triethylamine were
added. To this solution 200 mg (0.77 mmol) of 6,6A-[(1S)-1-methyle-
thyl]dioxy(aR)-1,1A-biphenyl-2,2A-diol 2 were added as solid over a period
of 30 min. After another 30 min of stirring at 278 °C the reaction mixture
was allowed to warm to room temperature and stirred for 2 h. The solution
was separated from solid triethylammonium chloride by filtration and the
solvent was removed in vacuo. After dissolving the white residue in 20 ml
of toluene and addition of 0.162 ml (0.117 g, 1.16 mmol) triethylamine, 0.06
ml (0.046 g, 0.77 mmol) isopropanol were added via a syringe. The reaction
mixture was stirred for 12 h at room temperature before it was filtered and
the solvent was removed under vacuum yielding 181 mg (68%) of a sticky
white solid.
3
, quantitative conversion and very good enantiomeric excesses
(ee) were achieved. The absolute stereochemistry for the
products of entries 1 and 2 were determined as (S)-alanine-N-
acetyl methyl ester and (R)-dimethyl-2-methylsuccinate re-
spectively by comparison with authentic samples when using 5
as the ligand.
Entry 6 shows good conversion, however the selectivity
reaches only 66% ee. Presumably due to the higher steric
demand of substrates 9 and 10 we only observed low ee values
with medium to high conversions (entries 3 and 5).
Substrate 11 was hydrogenated with complete conversion but
only medium ee.
Beside ligand 5 we synthesised its enantiomer, which was
also used in hydrogenation experiments showing identical
results with opposite stereoinduction.
The synthesis of phosphites containing other alcohols like
benzyl alcohol instead of isopropanol was also attempted. Due
to the formation of considerable amounts of side products,
isolation of the desired products is still challenging.
In conclusion, we have been able to synthesise new chiral,
non-racemic phosphite ligands by inducing the stereochemistry
1 A. Miyashita, A. Yasuda, H. Takaya, K. Toriumi, T. Ito, T. Souchi and R.
Noyori, J. Am. Chem. Soc., 1980, 102, 7932; A. Miyashita, H. Takaya, T.
Souchi and R. Noyori, Tetrahedron, 1984, 40, 1245.
2
M. J. Burk, Y. M. Wang and J. R. Lee, J. Am. Chem. Soc., 1996, 118,
142.
5
3
4
5
M. T. Reetz and G. Mehler, Angew. Chem., 2000, 112, 4047.
T. Harada, T. M. T. Tuyet and A. Oku, Org. Lett., 2000, 2, 1319.
M. J. Baker and P. G. Pringle, J. Chem. Soc., Chem. Commun., 1991,
1
292.
6 These latter phosphite comopounds are currently also under inverstiga-
tion as ligands for hydrogenation reactions.
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