DD275623A1 - PROCESS FOR THE PREPARATION OF NEW RHODIUM CARBOHYDRATEBIS (PHOSPHINITE) CHELATE CATALYSTS - Google Patents

Abstract

The invention relates to a process for the preparation of novel chiral rhodium-carbohydrate bis (phosphinite) chelate catalysts by producing these according to the invention by applying a Solvolysereaktion on new or known rhodium carbohydrate bis (phosphinite) chelates with protected by acetalization hydroxyl groups in the 4,6-position in which the solvolyseempfindlichen Phosphinigsaeureestergruppen are effectively protected by chelation. The new catalysts allow the achievement of particularly high enantioselectivities in asymmetric reactions and show very high activity.

Description

and R ¹ , R ² , R ³ , Ar, A ", L and k have the same meanings as in claim 1. Process according to claim 1, characterized in that the chelate catalysts I are present in situ or in substance according to equation (3) obtained intermediate neutral complexes III

^ Rh (L) _k (acac)? + (O - R - O) * ^ Rh (O - R - O) (acac) i + kL (3)

III and its subsequent transformation according to equation (4)

- R - 0) (acac) 7 + HA + kL

(4) Hacac

with the addition of the acid HA in a rapid reaction to release acetylacetone (Hacac) and re-incorporation of the ligands L into the cationic complexes II, finally, by their time-dependent solvolysis according to equation (2), the meaning of the symbols being the same as in claim 2 ,

4. The method according to claim 1 to 3, characterized in that the solvolysis is carried out in a solvent with good solubility for the complexes II such as tetrahydrofuran, 1,4-dioxane or dichloromethane and the precipitation by adding a solvent with low solubility for the target complexes I, such as diethyl ether, benzene, cyclohexane or n-pentane.

5. The method according to claim 1 to 3, characterized in that in addition to tetrahydrofuran, 1,4-dioxane or dichloromethane also alcohols such as methanol, ethanol or isopropanol or mixtures thereof find use as solvent for the Solvolyser-

Field of application of the invention

The invention relates to a process for preparing novel chiral rhodium oil chelate catalysts which catalyze C-C linking, hydroformylation, hydrosilylation, carbonylation and hydrogenation reactions. These enantioselectively active metal complex catalysts can be used for the preparation of optically active compounds which are used, for example, as chiral intermediates or bioactive agents such as pharmaceuticals, pheromones or sweeteners.

Characteristic of the known state of the art

It is known that numerous optically active phosphines, diphosphines, mono- and bisphosphinites (phosphinous esters), bisphosphinic acid amides or aminophosphine phosphinites can be used as ligands for asymmetric hydrogenations and other enantioselective reactions catalyzing metal complexes (JD Morrison [Ed.], Asymmetry Synthesis, Vol. 5, Chiral Catalysis, Academic Press, Orlando 1985). Thus, for example, rhodium chelates of P-chiral diphosphines form the basis of the Monsanto process for the preparation of L-dopa (US Pat. No. 4,008,281) A synthesis of chiral aminophosphine phosphinite chelates has recently been disclosed (DD-WP 253 947 A1).

Because of the easy representability of inexpensive starting material and the achievable high optical yields at high activity, carbohydrate bis (phosphinous acid ester) rhodium (I) chelates have proven particularly useful as a basis for the production of L-dopa (DD-WP 140036B1, DD-WP 248028A3) , Given the high suitability of the latter chiral rhodium (I) chelates with carbohydrate-bis (phosphinous ester) -type ligands, in which the residual carbohydrate hydroxyl functions are protected, for the asymmetric hydrogenation of 2-N-acylaminoacrylic acids with optical yields of more than 95% (S) -Aminosäurederivaten adheres to these chelates of the disadvantage that the enantioselectivity in the hydrogenation of analogous ester hardly exceeds 91%.

Aim of the invention

It is the object of the invention to develop a catalyst class with which in the hydrogenation of 2-N-Acylaminoacrylsäureestern equally high optical yields of at least 95% as in the analogous acids without loss of hydrogenation activity can be achieved.

Explanation of the essence of the invention

The object of the invention is to transform the ligand of Rhodiunvkohlhydratbi $ (phosphinite) chelate catalyst so that the catalyst in the asymmetric hydrogenation of (S) -amino acid derivatives ensures high optical yields without sacrificing the hydrogenation

The object of the invention is achieved by a process for preparing novel rhodium-carbohydrate bis (phosphinite) chelate catalysts of the general formula I

in the

R ^{1 is} alkyl, aralkyl, aryl, alkoxy, aralkoxy, aryloxy,

Ar Aryl,

A "an anion of an acid such as BFr, CICO ₄ ". SO ₄ H ", PF ₈ ", Cl ", R * -COO", R ⁴ SO ₃ ', where R ^{4 is} an alkyl or Ary Irest, L Alcohol, CO, olefin, diolefin and

k is a number between 0 and 3

mean,

in that according to the invention the chelate catalysts I prepared in solution in situ or in substance by precipitation with a slightly polar solvent in the carbohydrate ligand carry free hydroxyl groups in the 4- and 6-positions.

The preparation of the chelates I takes place according to the invention in a time reaction by acid-catalyzed solvolysis Rhodium chelates of the general formula II,

-Of ₁

in the

R ¹ , Ar, A ". L and k have the above meanings, R ^{2 is} an alkyl. Aralkyl or aryl radical and R ^{3 is} hydrogen, an alkyl, aralkyl or aryl radical

mean.

In this case, the highly solvolyseempfindlichen Phosphinigsäureestergruppen in the free state by chelation

with rhodium an effective protection, which is a particular feature of the invention, since the acid-catalyzed

Solvolysis of uncomplexed 2,3,0-bis (diarylphosphinite) carbohydrate ligands protected in 4,6-position not without Cleavage of the phosphinous acid groups is possible. According to the invention, the preparation of the chelate catalysts I is possible in two ways:

over in situ or in substance according to equation (1)

♦ (O - R - O)

Υ ^ h (L) _k (O - R -

II

obtained cationic starting complexes II and their time-dependent solvolysis according to equation (2), + HA

 »

+ 2H ₂ O

- (Y = O) I

where Y and R are parts of the chelating ligands in the above formula II:

-or.

via intermediary neutral complexes III obtained in situ or in substance according to equation (3)

y ^Y ^ s- ^Y > »

+ (O - R - O) - * ^ Rh (O - R - O) (acac27 + k L ₍₃₎

III

and their subsequent conversion according to equation (4)

- R - O) (acac27 + HA ♦ kL -> ^ Rh (O - R - O) (L). T ⁺ A "+ Hacac III

in rapid reaction by addition of acid with the release of acetylacetone (Hacac) and re-incorporation of the ligands L in the cationic complexes II, which in turn can be obtained preparatively intermediate by precipitation with low-polarity solvents or without isolation by further reaction according to equation (2) in time-dependent Solvolysis in the target complexes I can be transferred.

For the preparative recovery of the chelates I in substance, the starting complexes II and III are dissolved or formed in the minimum amount of a solvent with good solubility. Suitable solvents include ethers, such as tetrahydrofuran, 1,4-dioxane, ethylene glycol ethers and dichloromethane, as well as the production of a suspension is possible. Thereafter, the solvolysis to the target chelates I is started by adding hydrous acid. Particularly suitable acids are sulfuric acid, tetrafluoroboric acid, perchloric acid, hexafluorophosphoric acid, but also organic acids and sulfonic acids, the amount of acid and the necessary solvolysis time being related and resulting concretely from the examples. In this case, the amount of acid must be sufficient in the conversion of the neutral III complexes to set to form the cationic complexes II acetylacetone in freedom, so over 1 mole of acid HA per mole of chelate. The solvolysis times up to 100% solvolysis of the 4,6-O-acetal moieties of Il to the target complexes I result from the solvolysis sensitivity of the acetals, the concentration of catalyst acid and the reaction temperature and can within wide limits of a few minutes to over 10O hours The solvolysis is carried out at temperatures from room temperature to the boiling point of the solvent used. The cationic chelate catalysts I can then be precipitated by low solubility solvents for chelates (e.g., diethyl ether, benzene, cyclohexane, n-pentane). To obtain the chelates I in situ, one has greater freedom in the choice of solvents for carrying out the reaction and can also use alcohols, such as methanol, ethanol or isopropanol. In the processes according to Equation 1 or Equation 3, the chelation must be completed to Il or Ill, before the addition of acid, the solvolysis is initiated to the target complex I, otherwise the chelating ligands

0 - R - 0

solvolyze irreversibly at the Phosphinigsäureestergruppierungen.

According to the invention, chelates with a particularly solvolysis-sensitive group are suitable for carrying out the solvolysis

particularly suitable.

The new 4,6-0-isopropylidene-2,3> 0-bis (phosphinous acid ester) chelates, presented Ober the first produced 0-

or C-aryl-O-O-isopropylidene-.beta.-D-glucopyranosides, are to be used with advantage.

embodiments example 1 Preparation of PhenyM.e-CMsopropylidene-β-D-glucopyranoside

To a suspension of 32.3 g (126 mmol) of phenyl-.beta.-D-glucopyranoside in 11 anhydrous acetone is added 100 g of dry molecular sieve 3A and 1 g (0.52 mmol) of p-toluene sulfonic acid hydrate and 50 ml dimethoxypropane are added with stirring. 90 min is stirred at room temperature, filtered from the molecular sieve and made alkaline with 10 ml of concentrated aqueous ammonia solution. In the vacuum is largely concentrated, added 50 ml Pet ro let her and then brought to dryness. After dissolving in 100 ml of acetone and the addition of 50 ml of water is placed in a refrigerator overnight, clarified through a pleated filter and the filtrate again brought to dryness in vacuo. The residue is dissolved in 20 ml of hot acetone and cooled after adding 40 ml of diethyl ether. The colorless PhenyM ^ -O-isopropylidene-ß-D-glucopyranosid falls as a solvate with 1 mol of diethyl ether, 26.3 g (56% of theory), melting point 116 to 128 ° C (between 92 and 97 ° C melts previously part of the substance in the crystal ether), [a] § ⁶ -70.2 ° (ie acetone). The ether-free substance melts at 115.5 to 117.5 C ^4, IAU ⁵ -78.9 "(d. Acetone). Preparation of phenyl-4.6-0-isopropylidene-2.3-0-bis (diphenylphosphino) -β-D-glucopyranoside 10.7 g (36 mmol) of the ether-free PhenyM.sub.10-O-isopropylidene-.beta.-D-glucopyranoside are dissolved in 25.7 ml of absolute pyridine under anaerobic conditions and to the slightly heated solution are added 14, The solidifying reaction mixture is washed the next day with 50 ml of diethyl ether and then extracted several times with ether from a frit, the ethereal solution is concentrated to 60 ml, the crystalline target product appears in the refrigerator Recrystallization from diethyl ether to give 10.2 g of analytically pure PhenyM.eO-isopropylidene ^ .SO-bisldiphenylphosphinoJ-.beta.-D-glucopyranoside in 43% yield, mp. 144-147 ° C, [α] έ ⁵ -88.0 ° (c 2, CH ₂ Cl ₂ ).

Preparation of rhodium (IHZ, Z) -cycloocta-1,5-diene- [phenyl-2,3-O-bis (diphenylphosphino) -β-D-glucopyranoside tetrafluoroborate 310 mg (1 mmol) of rhodium (I) * (Z , Z) -cycloocta-1,5-diene-acetylacetonate and 665 mg (1 mmol) of the bisphosphinic acid ester described above are dissolved in 5 ml of tetrahydrofuran to chelate. Thereafter, solvolysis of the isopropylidene group is started by adding 0.51 ml (3.0 mmol) of 40% tetrafluoroboric acid with stirring

and after 215min by adding 20 ml of diethyl ether precipitated the yellow-orange target complex, which is present after analysis, filtration, washing with ether and drying. There are so 750 mg, d. H. 81% of theory, of a catalyst which results in hydrogenation of N-acyl-dehydroaminosäureestern to a maximum of 95.8% ee (S) -enantiomer.

Example 2

Analogously to Example 1, phenyl-C-.beta.-D-glucopyranoside (Hurd and Bonner, J. Am. Chem. Soc., 67 [1945], 1972) is converted to the corresponding 4,6-O-isopropylidene compound in 46% yield, mp. 152-153 ⁰ C, [α] "-13.2 ° (c1. acetone) and from 4.6 to 0-isopropylidene-2.3-0-bis (diphenylphosphino) -beta-D-glueopyranosylbenjen in 47% Yield recovered, m.p. 160-165 ° C, [α] "-25.1 ° (c 2, CH ₂ Clj). The Umsatt to RhodiumdMZ.ZI-cycloocta-i ^ -diene-We-O-isopropylidene ^ SO-bis (diphenylphosphino) -β-D-glucopyranosylbenzenHetrafluoroborat is carried out analogously to the O-phenyl-glucopyranosid derivative of Example 1, wherein the sol Volysezeit is extended to 330 min. The complex is obtained analytically in 66% yield and leads to a maximum of 94.6% ee (S) -2-N-Acylaminosäureestern.

Example 3

465 mg (1.5 mmol) of rhodium (I) - (Z, Z) -cycloocta-1,5-diene-acetylacetonate and 1.074 g (1.5 mmol) of phenyl-4,6-O- (R) -benzylidene-2,3 -O-bis (dlphenylphosphino) -β-D-glucopyranoside (according to OD-WP 248028 A3) are dissolved anaerobically in 1.5 ml of tetrahydrofuran. With stirring, 0.25 ml of 75% hexafluorophosphoric acid (2.15 mmol) is added. After 15 hours, precipitation is initiated by adding 6 ml of diethyl ether. The crystals are filtered, washed three times with ether and dried to obtain 1.04 g of a complex with a sharp melting point, mp. 171 to 172.5 ⁰ C and analysis C 54.15%, H, 5.03%, P8,3 %, Rh 9.85%, which would correspond to a 50% hydrolysis of the ligand (C ₄ H ₆ J ₅ Fe ₈ P ₃ Rh ₂ H ₂ O). The catalyst complex is in the IR spectrum two sharp OH bands at 3550 and 3610cm ^'1 and leads to a maximum of 94.4% ee (S) -2-N-Acylaminosäureestem.

Example 4 Analogously to Example 3, but by using 0.25 ml of 70% sulfuric acid (2.88 mmol), a complex in 75% iger Yield, which leads to a maximum of 95.2% ee (SW-N-Acylaminosäureestern. Examples

The catalyst of Example 4 can be used very advantageously shown in situ. To this end, under anaerobic conditions, 31.0 mg (0.1 mmol) of rhodium (IMZ, Z) -cycloocta-1,5-diene-acetylacetonate and 71.2 mg (0.1 mmol) of phenyl-4,6-O- ( R) -benzylidene-2,3-O-bis (diphenylphosphino) -β-D-glucopyranoside in 9.3 ml of tetrahydrofuran and after 10 min 0.7 ml of a freshly prepared solution of 0.35 ml of concentrated sulfuric acid in 25 ml Methanol (ie 0.14 mmol H ₃ SO ₄ in 0.7 mL). The solvolysis of the benzylidene grouping on the catalyst ligand now takes place in a time reaction, and after 10 hours a catalyst stock solution with 0.01 mmol rhodium chelate per ml is obtained which, in the case of hydrogenations, has a maximum enantioselectivity of 95.5% ee (S) -2-N-acylamino acid esters and is stable for at least 100 hours.

Examples

The same result as described in Example 5 is obtained when the catalyst stock solution is completely analogous but starting from 101.1 mg (0.1 mmol) of preformed cationic bisphosphinite complex rhodiumflMZ.Zt-cycloocta-IS-dien- (phenyl-4,6 -0- (R) -benzylidene-2,3-O-bis (diphenylphosphino (-β-D-glucopyranoside) -tetrafluoroborate in 9.8 ml of tetrahydrofuran with addition of 0.2 ml of the methanolic sulfuric acid from Example 5 (0.04 mmol H ₂ SO ₄ in 0.2 mol).

Example 7

Analogously to Example 6, except that the catalyst stock solution in 9.3 ml of tetrahydrofuran is added with the addition of 0.7 ml of methanolic acid containing 0.14 mmol sulfuric acid. Due to the increased acidity, the solvolysierte catalyst complex is formed after 3 hours, which can be seen by the high enantioselectivity of over 94% eebei the hydrogenation of 2-N-acyl-2,3-dehydroaminosäuren which is retained for at least 100 hours.

Example 8

Analogously to Example 7, except that the catalyst stock solution in 9.3 ml of methanol with the addition of 0.7 ml of methanolic sulfuric acid at 45 ⁰ C is set. The time required to form the solvolyzed catalyst complex is thus reduced to one hour.

Claims (2)

claims: 1. A process for the preparation of novel rhodium-carbohydrate bis-phosphinite-chelate catalysts of general formula I, in the R ^{1 is} alkyl, aralkyl, aryl, alkoxy, aralkoxy, aryloxy, Ar aryl, A "is an anion of an acid such as BF ₄ ", CIO ₄ ", SO ₄ H", PF ₆ ", Cl", R ⁴ -COO ", R ⁴ -SO ₃ -, wherein R ^{4 is} a Is alkyl or aryl radical,
L is alcohol, CO, olefin, diolefin and k is a number between 0 and 3
mean, characterized in that the chelate catalysts I prepared in solution in situ or in substance by precipitation with a low-polarity solvent in the carbohydrate ligand carry free hydroxyl groups in 4- and 6-position, and those protected from acid in the 4,6-position rhodium chelates of the general formula II in the R ¹ , Ar, A ", L and k have the above meanings, R ^{2 is} an alkyl, aralkyl or aryl radical and R ^{3 is} hydrogen, an alkyl, aralkyl or aryl radical, in a solvent or a solvent mixture by acid-catalyzed solvolysis in freedom, wherein the free state very solvololyseempfindlichen Phosphinigsäureestergruppierungen undergo effective protection by the chelation with rhodium. 2. The method according to claim 1, characterized in that the chelate catalysts I obtained in situ or in substance according to equation (1) cationic starting complexes II -KL and their time-dependent solvolysis according to equation (2) <R (0H) ₂ > _7 ⁺ A - (Y = O) getting produced, where Y ι and