Chiral organic catalysts based on chalcogen bond for activation of substrates and synthesis of optically active products

Abstract

: Chiral organic catalysts based on chalcogen bonding for the activation of substrates and the preparation of optically active products are derivatives of the optically active 1,1'-binaphthyl of formula I, which contain a chalcogen atom in their structure. Their use as compounds for the stereoselective synthesis of optically active molecules has been demonstrated and proved in a series of selected reactions in which the formation of optically active products in high yields and with high stereoselectivity has been observed.

Description

[0001] Chiral organic catalysts based on chalcogen bond for activation of substrates and synthesis of optically active products

[0002] Technical Field

[0003] The presented invention belongs to organic chemistry, material chemistry, and natural product chemistry. Its application extends into medicinal and industrial chemistry for the synthesis of chiral intermediates and final products.

[0004] State of the Art

[0005] To obtain optically active compounds, various methods are currently being developed that involve the isolation of natural enantiomerically pure products or employ organic synthesis using prochiral substrates and a suitable strategy during which a chiral center is formed.

[0006] Among the most important methods that enable the preparation of optically active products, the application of transition metal catalysis using chiral organic ligands dominates. This strategy enables highly efficient preparation of substances with high optical purity (for example Trost, B. M.; Van Vranken, D. L Asymmetric Transition Metal-Catalyzed Allylic Alkylations. Chemical Reviews 1996, 96 (1), 395-422; Shaw, S.; White, J. D. Asymmetric Catalysis Using Chiral Salen- Metal Complexes: Recent Advances. Chemical Reviews 2019, 119 (16), 9381-9426; Wen, J.; Wang, F.; Zhang, X. Asymmetric Hydrogenation Catalyzed By First-Row Transition Metal Complexes. Chemical Society Reviews 2021, 50 (5), 3211-3237), but the necessity of using transition metals together with strongly coordinating organic ligands disadvantages the wider application in conjunction with the now increasingly favored concept of "green chemistry."

[0007] The above-mentioned drawback is addressed by the concept of so-called organocatalysis, which is based on the application of a small organic molecule, often derived from a natural substance, that retains the catalytic ability to transform prochiral substrates to form optically active products (Antenucci, A.; Dughera, S.; Renzi, P. Green Chemistry Meets Asymmetric Organocatalysis: A Critical Overview On Catalysts Synthesis. ChemSusChem 2021, 14 (14), 2785- 2853). Optically active products are products which can rotate the plane of polarized light when the product contains an unequal amount of its stereoisomers

[0008] To date, the chiral organocatalysts used are most often derived from the amino acid L-proline, which is converted by suitable organic synthesis methods into the final form of the chiral organocatalyst. This organocatalyst has been used in the preparation of optically active polycyclic molecules or chiral products of condensation reactions and domino reactions of carbonyl compounds (for example Jiang, H.; Rodriguez-Escrich, C.; Johansen, T. K.; Davis, R. L.; Jorgensen, K. A. Organocatalytic Activation Of Polycyclic Aromatic Compounds For Asymmetric Diels-Alder Reactions. Angewandte Chemie International Edition 2012, 51 (41), 10271-10274; Raja, A.; Hong, B. -C.; Lee, G. -H. Organocatalytic Enantioselective Michael-Michael-Michael- Aldol Condensation Reactions: Control Of Five Stereocenters In A Quadruple-Cascade Asymmetric Synthesis Of Highly Functionalized Hexahydrophenanthrenes. Organic Letters 2014, 16 (21), 5756-5759). These and related organocatalysts work on the principle of forming a transient covalent intermediate with sufficient lifetime to enter the key stereodiscrimination step of the catalytic cycle. The stereodiscriminating step is defined as the step of the reaction which results in the formation of a chiral center in the product molecule. It is already clear from the principle of this method that its application is limited to substrates that are capable of forming sufficiently stable covalent intermediates with the catalyst molecule, while at the same time, it is necessary to ensure that the catalytically active species is recovered during the reaction.

[0009] The necessity for the formation of the mentioned covalent intermediate is effectively overcame by the application of i.e. non-covalent organocatalysts, which form a non-covalently bound complex between the active organocatalyst molecule and one or more reacting substrates during the stereodiscriminating step of the catalytic cycle. These non-covalent organocatalysts form non-covalent complexes with reacting molecules through non-covalent interactions, of which hydrogen bonding is the most widely used. These substances contain functional groups with a relatively acidic hydrogen atom in their structure which, through hydrogen bonding with the substrate, reduces its activation energy for the reaction in the key stereodiscrimination step of the catalytic reaction. This type of organocatalyst has been used in the synthesis of optically active polycyclic molecules or chiral products of condensation reactions and domino reactions of carbonyl compounds (for example Bera, K.; Schneider, C. Br0nsted Acid Catalyzed [3+2]- Cycloaddition Of 2-Vinylindoles With In Situ Generated 2-Methide-2 H -Indoles A ]lndoles: Highly Enantioselective Synthesis Of Pyrrolo[l,2- A ]lndoles. Chemistry ~ A European Journal 2016, 22 (21), 7074-7078Hodik, T.; Schneider, C. Boosted Acid-Catalyzed, Enantioselective Synthesis Of l,4-Dihydroquinoline-3-Carboxylates Via In Situ Generated Ortho- Quinone Methide Imines. Organic & Biomolecular Chemistry 2017, 15 (17), 3706-3716). It is clear from the principle of this method that its application is limited only to substrates that are capable of forming sufficiently stable non-covalent transition states between the active form of the organocatalyst and the reacting substrate, while none of the reaction components present (starting substances, reactants, excipients, products, intermediates, etc.) must be sensitive to the presence of Br0nsted acid.

[0010] The requirement for stability of the reactants and other components of the reaction under acidic (H+) conditions can be circumvented by using a different type of interaction to activate the reactants. This interaction is, among others, the so-called chalcogen bonding, which is mediated between a chalcogen atom (the chalcogen atoms considered are oxygen, sulfur, selenium, tellurium) and the activated substrate, which may be various carbonyl compounds, alcohols or organohalogenides.

[0011] From the state of the art, for example from the document Wang, W.; Zhu, H.; Liu, S.; Zhao, Z.; Zhang, L.; Hao, J.; Wang, Y. Chalcogen-Chalcogen Bonding Catalysis Enables Assembly Of Discrete Molecules. Journal of the American Chemical Society 2019, 141 (23), 9175-9179, there are known compounds derived from organophosphines that form cationic species with organic chalcogenides capable of catalyzing the multicomponent cyclization reaction of indole with polycarbonyl compounds to form products with potential axial chirality however no control of regio- and stereoselectivity was achieved. These organic molecules have been analogously applied in other works (Wang, W.; Zhu, H.; Feng, L.; Yu, Q.; Hao, J.; Zhu, R.; Wang, Y. Dual Chalcogen-Chalcogen Bonding Catalysis. Journal of the American Chemical Society 2020, 142 (6), 3117-3124; Yuan, X.; Wang, Y. A Selenide Catalyst For The Activation Of Alkenes Through Se--n Bonding. Angewandte Chemie International Edition 2022, 61 (27); Zhao, Z.; Pang, Y.; Zhao, Z.; Zhou, P. -P.; Wang, Y. Supramolecular Catalysis With Ethers Enabled By Dual Chalcogen Bonding Activation. Nature Communications 2023, 14 (1)).

[0012] From the state of the art, for example from the document Steinke, T.; Wonner, P.; Gauld, R. M.; Heinrich, S.; Huber, S. M. Catalytic Activation Of Imines By Chalcogen Bond Donors In A Povarov [4+2] Cycloaddition Reaction. Chemistry ~ A European Journal 2022, 28 (47), there are known compounds derived from cationic organocatalysts that contain a chalcogen atom attached to a triazolium ring being a positive charged. These achiral molecules have successfully catalyzed the Povarov reaction of aldimines with alkenes, but any attempts to stereoselectively control the course of the reaction have been unsuccessful.

[0013] From the state of the art, for example from the document Weiss, R.; Aubert, E.; Pale, P.; Mamane, V. Chalcogen-Bonding Catalysis With Telluronium Cations. Angewandte Chemie International Edition 2021, 60 (35), 19281-19286, there are known flexible cationic compounds derived from organic chalcogenides that catalyze the electrophilic aromatic halogenation of electron-rich aromatic compounds or mediate the catalysis of the Diels-Alder cycloaddition reaction.

[0014] The objective of the invention is to introduce a group of chiral catalytically active compounds containing a chalcogen atom in their structure, which overcomes the deficiencies of stereoselective organocatalysis resulting from the state of the art. The most significant deficiencies of the state of the art are the absence of chiral catalysts enabling the chemical transformation of acid-sensitive compounds or the necessity to use expensive and highly sensitive transition metal-derived catalysts together with labile chiral organic ligands.

[0015] Disclosure of the Invention

[0016] The subject invention is a derivative of optically active l,l'-binaftyl which contains a chalcogen atom in its structure, which overcomes the disadvantages of the current state of the art. The invention relates to the substance of formula I and its enantiomers, diastereomers, and mixtures of stereoisomers, as well as to their use as intermediates for the preparation of catalysts derived therefrom and for the preparation of optically active products.

[0017] Thus, the invented compounds can be used according to the invention as catalysts of chemical reactions for the preparation of optically active products. The advantages of these invented catalysts are optical purity, simple and robust preparation, high stability and catalytic activity mediated by the chalcogen bond between the chalcogen atom and the reacting substrate. This interaction is particularly desirable for substrates that are unstable in Br0nsted acid environments or for the activation of halogenated organic molecules.

[0018] The stereoselective catalytic activity of the compounds according to the invention was demonstrated and proved on the addition reaction of nitromethane to tert-butyl (l-allyl-2- oxoindolin-3-ylidene)carbamate in the presence of a catalytic amount of the inorganic base. This reaction gave rise to the optically active product tert-butyl-(S)-(l-allyl-3-(nitromethyl)-2- oxoindolin-3-yl)carbamate in nearly quantitative yield (99% yield). The stereoselectivity of the reaction was determined by high-performance liquid chromatography using chiral stationary phase columns, and it was found to be 95:5 e.r. in favor of the 5 configurated product.

[0019] Another example of stereoselective catalytic activity of compounds according to the invention was demonstrated and shown on the addition reaction of 1,3-dicarbonyl compounds, e.g., acetylacetone, with tert-butyl (l-benzyl-2-oxoindolin-3-ylidene)carbamate in the presence of a catalytic amount of an inorganic base. This reaction gave rise to the optically active product in high yield (96% yield). The stereoselectivity of the reaction was determined by high- performance liquid chromatography using chiral stationary phase columns, and it was found to be 80:20 e.r. in favor of the R configurated product.

[0020] Another example of stereoselective catalytic activity of compounds according to the invention was demonstrated and shown on the addition reaction of diethyl malonate with tert-butyl (1- benzyl-2-oxoindolin-3-ylidene)carbamate in the presence of a catalytic amount of an inorganic base. This reaction gave rise to the optically active product in high yield (96% yield). The stereoselectivity of the reaction was determined by high-performance liquid chromatography using chiral stationary phase columns, and it was found to be 92:8 e.r. in favor of the R configurated product.

[0021] Brief description of the Drawings

[0022] Figure 1 shows the results of HPLC analysis of the reaction of nitromethane with tert-butyl (Z)- (l-allyl-2-oxoindolin-3-ylidene)carbamate. The upper chromatogram demonstrates the results of HPLC analysis of the racemic standard product (compound II), which was prepared in the absence of the compound of formula I. The lower chromatogram demonstrates the results of HPLC analysis of the optically active product (compound II), which was prepared in the presence of the compound of formula I as a catalyst. (Conditions for analysis - AD-3R column; 70% hexane / 30% / -propanol v / v; 1.0 mL / min; 254 nm).

[0023] Figure 2 shows the results of HPLC analysis of the reaction of acetylacetone with tert-butyl (Z)- (l-benzyl-2-oxoindolin-3-ylidene)carbamate. The upper chromatogram demonstrates the results of HPLC analysis of the racemic standard product (compound III), which was prepared in the absence of the compound of formula I. The lower chromatogram demonstrates the results of HPLC analysis of the optically active product (compound III), which was prepared in the presence of the compound of formula I as a catalyst. (Conditions for analysis - OD-3 column; 90% hexane / 10% / -propanol v / v; 1.0 mL / min; 250 nm).

[0024] Figure 3 shows the results of HPLC analysis of the reaction of diethyl malonate with tert-butyl (Z)-(l-benzyl-2-oxoindolin-3-ylidene)carbamate. The upper chromatogram demonstrates the results of HPLC analysis of the racemic standard product (compound IV), which was prepared in the absence of the compound of formula I. The lower chromatogram demonstrates the results of HPLC analysis of the optically active product (compound IV), which was prepared in the presence of the compound of formula I as a catalyst. (Conditions for analysis - AD-3R column; 70% hexane / 30% / -propanol v / v; 1.0 mL / min; 256 nm).

[0025] Example 1

[0026] Example 1 shows the synthesis and characterization of the compound of formula I - (R)-5,5'- diphenyl-5 / - / ,5' / - / -[6,6'-bibenzo[b]naphtho[2,3-c / ]selenophene]-5,5'-diium trifluoromethanesulfonate.

[0027] A flame dried round bottom flask was charged with enantiomerically pure (R)-l,l-bi(2-naphtol) (30 g; 117.4 mmol; 1.0 eq), 2-bromopropionamide (48 g; 352.2 mmol; 3.0 eq), K2CO3(44 g; 352.2 mmol; 3.0 eq), KI (1.7 g; 11.7 mmol; 0.10 eq.) and dry DMSO (587 mL). The resulting mixture was stirred at 50 °C for 24 hours. Subsequently, the reaction flask was lifted up from the oil bath, and potassium hydroxide (73.6 g; 1467.6 mmol, 12.5 eq.) was added directly to the reaction flask. The flask was then reimmersed into the preheated oil bath at 150 °C and stirred vigorously for 4 hours. The reaction mixture was then cooled to room temperature and poured into another flask containing water (3 L). Precipitates were allowed to settle down, washed several times with water, and dried under vacuum. This procedure provided 21.6 g (65%) ( / ?)- l,l'-binaphthalene-2,2'-diamine as a white foamy solid.

[0028] To a mixture of ( / ?)- l,l'-binaphthalene-2,2'-diamine (3.38 g; 11.9 mmol) and Raney Ni-AI alloy (23.9 g) in isopropanol (400 mL) and water (400 mL) was gradually added 3 wt-% aqueous NaOH solution (800 mL) via an addition funnel over a period of 2 hrs at 90 °C. After 36 h of vigorous stirring at 90 °C, the reaction mixture was cooled to room temperature. The mixture was filtered through Celite pad. After filtration was complete, the filter cake was washed thoroughly with ethyl acetate. (Caution: The Celite pad should never dry out during filtration as there is a risk of ignition of the activated form of the hydrogenation catalyst.) The filtrate was then extracted with ethyl acetate, dried over MgSO4 and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel (hexane / ethyl acetate; 3:1 v / v) as eluent to afford 2.89 g (84%) of ( / ?)-5,5',6,6',7,7',8,8'-octahydro-l,l'-binaphthalene-2,2'- diamine product as a white solid.

[0029] To a stirred solution of ( / ?)-5,5',6,6',7,7',8,8'-octahydro-l,l'-binaphthalene-2,2'-diamine (12.2 g; 41.7 mmol; 1.0 eq) and CaCO3(12.6 g; 125.1 mmol; 3.0 eq) in MeOH (85 mL) benzyltrimethylammonium dichloroiodate (29.1 g, 83.4 mmol; 2.0 eq) was added at 0 °C. The reaction was stirred for 2 h at ambient temperature. After this period, the mixture was quenched with a saturated NaHCO3solution (400 mL) and a saturated Na2SO3solution (400 mL) at 0 °C. The resulting mixture was extracted with dichloromethane (2 x 300 mL). The combined organic layers were washed with brine, dried over MgSO4, and concentrated under reduced pressure. The resulting residue was purified by flash column chromatography on silica gel (hexane / ethyl acetate; 3:1 v / v) to afford 18.2 g (80%) of ( / ?)-3,3'-diiodo-5,5',6,6',7,7',8,8'- octahydro-l,l'-binaphthalene-2,2'-diamine as a light yellow solid.

[0030] To a stirred solution of ( / ?)-3,3'-diiodo-5,5',6,6',7,7',8,8'-octahydro-l,l'-binaphthalene-2,2'- diamine (17.8 g; 32.7 mmol; 1.0 eq) in benzene (655 mL) at 80 °C was added portionwise DDQ (3.34 g; 14.7 mmol; 0.45 eq) along with MnO2(34.1 g; 393 mmol; 12 eq). Within 5 hours, DDQ and MnO2were gradually added till the final contain of 0.90 eq of DDQ and 24 eq. MnO2. Upon complete consumption of the starting material, the reaction mixture was cooled to room temperature and subsequently filtered through a Celite pad, utilizing ethyl acetate as the eluent. Filtrate was then concentrated under reduced pressure, and the crude mass was purified by flash column chromatography on silica gel (DCM / hexane; 1:1 v / v) to afford 12.66 g (72%) of (R)-3,3'-diiodo -l,l'-binaphthalene-2,2'-diamine as a light brown solid.

[0031] Mixture of (R)-3,3'-diiodo -l,l'-binaphthalene-2,2'-diamine (3.0 g; 5.6 mmol; 1.0 eq), Pd(PPh3)4(647 mg, 0.55 mmol; 0.10 eq), KHCO3(3.36 g, 33.6 mmol; 6.0 eq) and 2- phenylselanylphenylboronic acid (6.2 g, 22.4 mmol; 4.0 eq) in degassed dioxane (70 mL) and H2O (7 ml) was stirred at 80 °C for under an argon atmosphere. After cooling to room temperature, the resulting mixture was poured into water (50 mL) and extracted with ethyl acetate (2 x 100 mL). The combined organic layers were washed with brine, dried over MgSO4, and concentrated. The residue was purified by flash column chromatography on silica gel (EtOAc / hexane, 1:10 v / v) to afford 3.64 g (87%) of ( / ?)-3,3'-bis(2-phenylselanylphenyl)-l,l'- binaphthalene-2,2'-diamine as a light yellow solid.

[0032] Trifluoromethanesulfonic acid (178 pL; 4.0 mmol; 4.0 eq) was added dropwise to a suspension of ( / ?)-3,3'-bis(2-phenylselanylphenyl)-l,l'-binaphthalene-2,2'-diamine (750 mg; 1.0 mmol; 1.0 eq) in a mixture of EtOH (0.6 mL) and acetonitrile (6.0 mL) at 0 °C. Stirring was kept for 5 minutes at -20 °C followed by isopentyl nitrite (141 pL; 2.1 mmol; 2.1 eq) addition. The resulting mixture was stirred at -20 °C for 40 minutes. The reaction mixture was then dried under reduced pressure in ambient conditions. The residue was resuspended in minimal amount of CHCI3 (~1 mL), and the diazonium salt was precipitated by adding cold diethyl ether (20 mL). The precipitated diazonium salt was then isolated by filtration, redissolved in CHCI3(20 mL), and stirred at 60 °C until the N2gas evolution significantly diminished (around 45 minutes). The reaction solvent was removed under reduced pressure, and the resulting residue was purified by flash column chromatography on silica gel (DCM only to DCM / MeOH, 20 / 1 v / v) to afford 610 mg (60%) of the compound of formula I, i.e., of (R)-5,5'-di phenyl-5 / - / ,5' / - / -[6,6'- bibenzo[b]naphtho[2,3-c / ]selenophene]-5,5'-diium trifluoromethanesulfonate as a light brown solid.

[0033] ( / ?)-5,5,-Diphenyl-5 / - / ,5, / - / -[6,6,-bibenzo[fa]naphtho[2,3-c / ]selenophene]-5,5,-diium trifluoromethanesulfonate (I)

[0034] Rf = 0.2 (dichloromethane / methanol, 20:1 v / v). a2Ds= +46.0 (c = 1.0; CHCI3).

[0035] XH NMR (600 MHz, CDCI3): 6 6.25 (dd, J = 8.5 Hz, 1H); 6.61 (ddd, J = 8.1, 6.8, 1.1 Hz, 1H); 6.65-6.66 (m, 1H); 6.71-6.72 (m, 1H); 6.78 (ddd, J = 8.3, 6.8, 1.2 Hz, 1H); 6.92 (dd, J = 8.5, 7.3 Hz, 1H); 6.95-6.98 (m, 3H); 7.18-7.24 (m, 3H); 7.28-7.30 (m, 1H), 7.41 (d, J = 8.5 Hz, 1H); 7.48-7,52 (m, 1H); 7.56-7.61 (m, 1H); 7.63-7.66 (m, 1H); 7.84-7.95 (m, 3H); 8.14 (dd, J = 30.4, 8.2 Hz, 2H); 8.21-8.24 (m, 1H); 8.37-8.55 (m, 3H); 8.85-8.90 (m, 2H).

[0036] 19F NMR (564 MHz, CDCI3): 6 -78.34.

[0037] 13C NMR (150 MHz, CDCI3): 6 119.4; 121.5; 124.4; 124.5; 125.0; 125.1; 125.6; 125.7; 126.9; 127.5; 128.3; 128.5; 129.0; 129.1; 129.5; 129.8; 129.9; 130.0; 130.1; 130.4; 130.8; 131.0; 131.1; 131.3; 131.4; 131.8; 132.3; 132.5; 132.6; 133.0; 133.1; 133.4; 133.7; 134.1; 134.3; 134.4; 134.9; 135.1; 135.2; 135.4; 135.5; 135.7; 136.1; 136.3; 136.5; 136.9; 140.5; 141.8; 142.1.

[0038] 77Se NMR (114 MHz, CDCI3): 6494.3; 495.6; 503.3.

[0039] MS (APCI+; m / z): calculated for C38H23Se2+[M - C6H5]+: 639.0; found: 638.9. calculated for C32Hi9Se2+[M - C6H5- C6H5+ H]+: 563.0; found: 562.8. Example 2

[0040] Example 2 shows the result of the catalytic activity of the substances according to the invention for the preparation of optically active products of formula II - tert-butyl-(S)-(l-allyl-3- (nitromethyl)-2-oxoindolin-3-yl)carbamate. tert-Butyl-(Z)-(l-allyl-2-oxoindoline-3-ylidene)carbamate (43 mg; 0.15 mmol; 1.0 eq), K2CO3(0.21 mg; 1 mol %), and catalyst of formula I (1.52 mg; 1 mol-%) were placed into the screw capped tube under argon atmosphere, and the tube was brought to -20 °C. Then added nitomethane (41 pL; 0.75 mmol, 5.0 eq) and dry THF (1.0 mL; 0.15 M) and the reaction mixture was stirred at -20 °C for 36 hours. After full consumption of the starting material, the reaction was quenched by the addition of water (2 mL), followed by extraction with EtOAc (2 x 2 mL). Evaporation of the solvent under reduced pressure provided the crude product, which was purified by flash column chromatography on silica gel (hexane / EtOAc, 4 / 1 v / v) to afford 51 mg (99 %) of tert-butyl-(S)-(l-allyl-3-(nitromethyl)-2-oxoindoline-3-yl)carbamate as a white solid. tert-Butyl-(S)-(l-allyl-3-(nitromethyl)-2-oxoindolin-3-yl)carbamate (II)

[0041] Rt = 0,4 (hexane / ethyl acetate, 4:1 v / v). e.r.: 95:5 (90 % e.e.); c = +4.0 (c = 1.0; CHCI3).

[0042] XH NMR (600 MHz, CDCI3): 6 1.34 (s, 9H); 4.31 (d, J = 16.2 Hz, 1H); 4.47 (dd, J = 16.2, 5.2 Hz, 1H); 4.64 (d, J = 12.4 Hz, 1H); 4.99 (d, J = 12.4 Hz, 1H); 5.27 (d, J = 10.3 Hz, 1H); 5.35 (d, J = 17.3 Hz, 1H); 5.83-5.89 (m, 2H); 6.89 (d, J = 7.9 Hz, 1H); 7.08 (t, J = 7.6 Hz, 1H); 7.34 (t, J = 7.8 Hz, 1H); 7.47 (d, 7 = 7.5 Hz, 1H).13C NMR (150 MHz, CDCI3): 6 28.2; 43.1; 59.9; 76.9; 77.1; 77.3; 77.8; 81.3; 109.9; 118.44; 123.5;

[0043] 124.7; 125.9; 130.4; 130.8; 142.7; 153.8; 172.7.

[0044] HPLC: CHIRALPAK AD-3R column; 70 % hexane / 30 % / -propanol v / v; 1.0 mL / min; 254 nm; Rti-

[0045] 4.9 min, Rt2- 6.6 min.

[0046] The results of HPLC analysis are shown in Figure 1.

[0047] Example 3

[0048] Example 3 shows the result of the catalytic activity of the substances according to the invention for the preparation of optically active products of formula III - tert-butyl-(R)-(l-benzyl-3-(2,4- dioxopentane-3-yl)-2-oxoindoline-3-yl)carbamate. tert-Butyl-(Z)-(l-benzyl-2-oxoindoline-3-ylidene)carbamate (16.5 mg; 0.05 mmol; 1.0 eq), K2CO3(1.0 mg; 0.0075 mmol; 0.15 eq), and catalyst of formula I (0.005 mmol; 0.10 eq) were placed into the screw capped tube under argon atmosphere, and the tube was brought to 0 °C. Then added acetylacetone (12 pl; 0.10 mmol; 2.0 eq) and dry toluene (2.0 mL) and the reaction mixture was stirred at 0 °C for 20 hours. After full consumption of the starting material, the reaction was filtered through a pad of Celite. Evaporation of the solvent under reduced pressure provided the crude product, which was purified by flash column chromatography on silica gel (hexane / EtOAc, 4 / 1 v / v) to afford 21 mg (96 %) of tert-butyl-(S)-(l-benzyl-3-(2,4- dioxopentane-3-yl)-2-oxoindoline-3-yl)carbamate as a yellowish oil. tert-butyl-( / ?)-(l-benzyl-3-(2,4-dioxopentane-3-yl)-2-oxoindoline-3-yl)carbamate (III)

[0049] Rf = 0.3 (hexane / ethyl acetate, 4:1 v / v). e.r.: 80:20 (60 % e.e.); a = +2.0 (c = 1.0; CHCI3).

[0050] XH NMR (600 MHz, CDCI3): 6 1.31 (br s, 9H); 2.16 (s, 3H); 2.30 (s, 3H); 4.07 (br s, 1H); 4.83 (br s, 1H); 5.04 (d, J = 15.7 Hz. 1H); 6.58 (s, 1H); 6.72 (d, J = 7.8 Hz, 1H); 6.98 (td, J = 7.6, 1.1 Hz, 1H); 7.18 (td, J = 7.7, 1.3 Hz, 1H); 7.26-7.29 (m, 2H); 7.35 (t, J = 7.6 Hz, 2H); 7.41 (d, J = 7.4 Hz, 2H).

[0051] HPLC: CHIRALPAK OD-3 column; 90 % hexane / 10 % / -propanol v / v; 1.0 mL / min; 250 nm; Rti- 2.3 min, Rt2- 2.7 min.

[0052] The results of HPLC analysis are shown in Figure 2.

[0053] Example 4

[0054] Example 4 shows the result of the catalytic activity of the substances according to the invention for the preparation of optically active products of formula IV - diethyl-( / ?)-2-(l-benzyl-3-((tert- butoxycarbonyl)amino)-2-oxoindoline-3-yl)malonate. tert-Butyl-(Z)-(l-benzyl-2-oxoindoline-3-ylidene)carbamate (16.9 mg; 0.05 mmol; 1.0 eq), K2CO3(1.0 mg; 0.0075 mmol; 0.15 eq), and catalyst of formula I (0.005 mmol; 0.10 eq) were placed into the screw capped tube under argon atmosphere, and the tube was brought to 0 °C. Then added diethyl malonate (16 pl; 0.10 mmol; 2.0 eq) and dry dichloromethane (2.0 mL) and the reaction mixture was stirred at 0 °C for 48 hours. After full consumption of the starting material, the reaction was filtered through a pad of Celite. Evaporation of the solvent under reduced pressure provided the crude product, which was purified by flash column chromatography on silica gel (hexane / EtOAc, 4 / 1 v / v) to afford 26 mg (99 %) of diethyl-( / ?)-2-(l- benzyl-3-((tert-butoxycarbonyl)amino)-2-oxoindoline-3-yl)malonate as a yellowish oil. diethyl-( / ?)-2-(l-benzyl-3-((tert-butoxycarbonyl)amino)-2-oxoindoline-3-yl)malonate (IV)

[0055] Rf= 0.2 (hexane / ethyl acetate, 4:1 v / v). e.r.: 92:8 (84 % e.e.); a ,9= +11.1 (c = 0.9; CHCI3).

[0056] XH NMR (600 MHz, CDCI3): 6 1.19 (t, J = 7.1 Hz, 3H); 1.19 (t, J = 7.1 Hz, 3H); 1.31 (s, 9H); 3.92 (s, 1H); 4.14-4.18 (m, 4H); 4.87 (br s, 1H); 5.00 (d, 7=15.6 Hz, 1H); 6.45 (s, 1H); 6.70 (d, J = 7.8 Hz, 1H); 6.96-6.99 (m, 1H); 7.16-7.19 (m, 1H); 7.24-7.28 (m, 1H); 7.32 (ddd, J = 7.7, 6.6, 1.4 Hz, 2H); 7.39 (d, J = 7.5 Hz, 1H); 7.42 (d, J = 8.2 Hz, 2H).

[0057] HPLC: CHIRALPAK AD-3R column; 70 % hexane / 30 % / -propanol v / v; 1.0 mL / min; 256 nm; Rti= 4.9 min, Rt2- 6.2 min.

[0058] The results of HPLC analysis are shown in Figure 3.

[0059] Industrial applicability

[0060] Catalytically active derivatives of optically active l,l'-binaphthyl, which contain a chalcogen atom in their structure, are industrially useful in the production of optically active intermediates in chemical syntheses and final optically active products.

Claims

CLAIMS1. A derivative of optically active l,l'-binaftyl containing in its structure a chalcogen atom of formula I and its enantiomers, diastereomers and mixtures of stereoisomers.

2. Derivatives of formula I according to claim 1 for use as intermediates in the preparation of catalysts derived therefrom.

3. Derivatives of formula I according to claim 1 for use in the preparation of optically active products.

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