CS201352B1 - Process for preparing 2,3 -0-isopropyliden-2,3-dihydroxy-1,4-bis/diphenylphosphine/butane - Google Patents

Description

BACKGROUND OF THE INVENTION The present invention relates to a process for the preparation of 2,3-di-propylidyl-2,3-dihydroxy-1,4, bis (diphenylphosphino) butane as a catalyst required for the asymmetric hydrogenation of acetylderivatives of α, (3-unsaturated α-amino acids to L - and amino acids.

α, β - unsaturated α-amino acids are precursors of important α-amino acids and their hydrogenation is currently of great importance due to the latest production of L-amino acids.

It is known that asymmetric homogeneous / hydrogenation is successfully carried out in the presence of Group 8 transition metal complexes which contain a chiral ligand in their coordination sphere. The highest optical yields were obtained with chiral diphosphine complexes prepared in situ from an olefinic complex, rhodium of the type Rh (en) ₂ Cl ₂ and 2,3-O-isopropylidene (or cyclohexylidene or cyclopentylidene) -2,3-dihydroxy- 1,4-bis (diphenylphosphino) butane. This diphosphine is known as DIOP (Kagan H, Dang T .: J. Amer. Chem. Soc. 94, 6429 (1972)).

When using a catalyst with (-) - DIOP as a chiral component, N-acetylamino-cinnamic acid yields DN-acetylphenylalanine (R configuration), while (-j -) - DIOP with the reverse configuration to both chiral carbon atoms.

In the synthesis of (-) - DIOP, the key chiral intermediate is 2,3-O-isopropylidene-Lthreitol, prepared from L - (+) - tartaric acid, readily available from natural material. D - (-) - tartaric acid, on the other hand, is to be obtained by resolution of racemic tartaric acid into optical antipodes, the preparation of racemates being difficult in itself (eg hydroxylation of maleic or fumaric acid or racemization of L - (- j -) - tartaric acid).

The present invention relates to a process for the preparation of 2,3-O-isopropylidene-2,3-dihydroxy-1,4-bis (diphenylphosphino) butane, characterized in that 2,3-O-isopropylidene-Dthreitol is treated at a temperature of -10 to + 10 ° C with 4-toluenesulfochloride, preferably in pyridine, and then with sodium diphenylphosphine at a temperature of from 10 to 40 ° C. The product obtained is used to prepare a catalyst for asymmetric homogeneous hydrogenation of N-acyl derivatives of α, β-unsaturated α-amino acids to L-α-amino acids.

The reaction is illustrated by the following scheme:

The invention is illustrated by the following example:

Example

To a solution of 8.4 g of isopropylidenthreitol in 55 ml of dry pyridine at 0 ° C was added 21 g of triturated 4-toluenesulfochloride at once, the mixture was shaken until dissolved and kept at 0 ° C for 12 hours. After pouring on ice, the crystals were aspirated, washed with cold ethanol and recrystallized from ethanol. 17.1 g of the product of 1.1 were obtained. 92-94 ° C / "/ ²⁰ d / - 12.2 ° (c 3.5 CHC1 _3). 2,3-O-isopropylidene-2,3-dihydroxy-1,4-bis (diphenylphosphino) butane.

A solution of 10 g of ditosylate in 30 ml of tetrahydrofuran was added dropwise with stirring to a solution of sodium diphenylphosphine. After stirring for 2 hours, the salt was filtered, washed with benzene, the filtrate was concentrated and the residue was poured over with ethanol. The precipitated crystals were recrystallized from ethanol, m.p. Mp 88-89 ° C.

OBJECT OF THE INVENTION

Claims (1)

A process for the preparation of 2,3-O-isopropylidene-2,3-dihydroxy-1,4-bis (diphenylphosphino) butane, characterized in that the 2,3-O-isopropylidene-Dthreitol is treated at a temperature of from -10 to 10 ° C. -10 ° C with 4-toluenesulfochloride and then with sodium diphenylphosphine at a temperature of from 10 to 40 ° C.