MXPA99004103A - Bissteroidal compounds and their use for the preparation of chiral complexes - Google Patents

Abstract

Bissteroidal compounds of general formula (I), in which R1 stands for hydrogen, alkyl, acyl, fluorine, and X1R5, where X1 stands for oxygen and sulfur and R5 can either be hydrogen, alkyl, aryl;R2 stands for hydrogen and alkyl;the stereochemistry of C-13, C-14 and C-17 may either be a or b;X stands for oxygen, hydroxyl, trifluormethylsulfonyloxy, or (R6)2P, where R6 can be aryl, alkyl and cycloalkyl;R3 stands for hydrogen, alkyl, aryl, trialkylsilyl, fluorine and X2R6, where X2 stands for oxygen and sulfur and R6 stands for hydrogen, trifluormethylsulfonyl, alkyl, cycloalkyl or aryl. R4 can either be a substituent in the 6 or 7 position of the steroid with the meaning of hydrogen, alkyl, aryl, fluorine, and X3R7, where X3 stands for oxygen, sulfur or trialkylsilyl and R7 stands for hydrogen, trifluormethylsulfonyl, alkyl or aryl, and the B-ring of the steroid contains none or two double bonds. Enantio- and Diastereomeric derivatives of compounds of general formula (I), metal complexes thereof and their use in enantioselective reactions.

Description

BISESTEROIDAL COMPOUNDS AND THEIR USE FOR THE PREPARATION OF QUIRAL COMPLEXES DESCRIPTION OF THE INVENTION The invention relates to b i s t ero idale s compounds and their use for the preparation of chiral complexes, useful as catalysts for various asymmetric syntheses.

BACKGROUND OF THE INVENTION Chiral 2, 2 '-bis-diphenylphosphino-1,1' -bi-2-naphthol (BINAP) introduced by Noyori (J. Am. Chem. Soc. 1980, 102, 7932) in 1980 was found which has wide application as a chiral ligand in laboratory asymmetric catalysis superior to the industrial scale. The major drawbacks of the Noyori-BINAP synthesis are a bromide reaction of 240 ° C at 320 ° C and a delayed resolution step of a BINAP precursor by crystallization with either sulfonic acid acid or acid 2,3- 0-diben zoi 11 ar t ar as a resolving agent, providing a low overall yield of the desired reagent (Nachr. Chem. Techn.Lab. 1996, 44, 996).

A new procedure by Verhoeven (US Pat. No. 5,399,771) evading the tedious introduction of the group di f eni 1 fo s f ina and providing an easy preparation of BINAP by catalytic nickel phosphorylation of the corresponding ditriflate of 1 '1 -Bi-2 -na f t o 1 (BINOL) However, their improved BINAP syntheses are still based on the resolution of BINOL with trans1, 2 -di-amino-clohexane as a resolving agent (J. Org. Chem. 1986, 51, 629). Although the spheroids are interesting in interesting compounds for asymmetric catalysis due to their rigid structure, the synthesis of 4,4'-is (es t ero ides) and any application of them as chiral ligands in asymmetric catalysis is unprecedented until now. The present invention describes the synthesis di es te reo s the ec ti va of (Ra) - and (Sa) -4,4 '-bis (3-di f iofos f inoes tra-1, 3, 5 (10) , 6, 8 -pent aeno) and the application of these new biphosphines as chiral ligands in metal complexes for the enantioselective hydrogenation of β-acids that toes tere s, a-β-unsaturated and dehydroamino acid s.

DETAILED DESCRIPTION OF THE INVENTION The Bis compounds are eroidal, of the general formula I I in which Rj. represents hydrogen, alkyl, acyl, f l or r, and X 1 R5, where Xi represents oxygen and sulfur and R5 can be any of hydrogen, alkyl, aryl, R2 represents hydrogen and alkyl; the stereochemistry of C-13, C-14 and C-17 can be any of a or X represents oxygen, hydroxyl trifluoro and tyl sulphonyloxy, or (Re): P, where Rd can be aryl, alkyl and cycloalkyl, R3 represents hydrogen, alkyl, aryl, trialkyl, fluoro, and X2Rβ, wherein X2 represents oxygen and sulfur and R represents hydrogen, trifluoromyl sulphonyl, alkyl, cycloalkyl or aryl. R may be any substituent in the 6 or 7 position of the spheroid with the meaning of hydrogen, alkyl, aryl, fluorine, and X3R7 where X3 represents oxygen, sulfur or other 1 if 1 and R7 represents hydrogen, tif luoromethyl sulf onyl, alkyl or aryl, and the B-ring of the spheroid containing no or two double bonds The Enantio- and D i -te derivatives of the compounds of the general formula I. The alkyl radical of I1-R7 have the meaning of lower alkyl substituents, for example the methyl-, ethyl-, propyl-, 2-methylethyl-, 2-me ti 1-propi 1 -, 3 -me t il-p rop i 1 -, 2,2 group -dimet i 1-et il-, or butyl The acyl radical of Ri has the meaning of C1-C6- groups, for example, acyl-, pro-onyl, 1-co-, butyric or hexanoic group The radical of the aryl group of R., R 4, R 5, R 6 and 7 have the meaning of phenyl-, benzyl- or 4-methylphenyl substituents The cycloalkyl radical of Rc has the meaning of a cyclop group ethyl or cyclohexyl. The trialkyl radical 1 s i 1 i of R 3 or X 3 has the meaning of trimethyl- or tert-butyldimethylsilyl. The 3-hydroxy-1,3,5,5 (10) 6,8-estrapentaen-17-one (Equi 1 eni) 1 is supplied at the standard conditions of a reduction Wo 1 ff -Kishne r (J. A. Chem. Soc. 1946, 68, 2487) giving Estra-1, 3, 5 (10), 6, 8-pentaen-3-ol 2 in 80-85% of r endimi ent.

The targets (Ra) - and (Sa) -4,4 '-bis (Estra-1, 3, 5 (10), 6, 8-pentaen-3-ol) (bisequinol) 3 are preparations of Es tr a- 1, 3, 5 (10), 6, 8 -pent aen-3-or 1 2 by phenolic coupling of catalysed metal Coupling is performed with catalytic amounts of a copper-amine complex in methylene chloride under a nitrogen atmosphere (Tetrahedron Lett., 1994, 35, 7983), generating the di re as s-3 and R-3. In contrast to the synthesis of Noyori BINOL these two di eromers can be easily separated by flash chromatography thus avoiding the prolonged resolution of enantiomers with an additional resolving agent. The absolute configuration of the new ligands (Ra) -y (Sa) -4,4 '-bis (Estra-1, 3, 5 (10), 6, 8 -pen t aen- 3 - or 1) 3, ( Ra) - and (Sa) -4,4 '-bis (Estra-1, 3, 5 (10) -trien-3-ol) 5 and (Ra) - and (Sa) - 4, 4' -bi s (3-di f 1 i fos f inoe st a-1, 3, 5 (10), 6, 8 -pent aen) 7 where determined by CD spectroscopy in comparison to the CD spectrum of the ligand (Ra) -bis (17- beta-methoxyestra-l, 3,5 (10) -trien-3-ol) R-4 whose absolute configuration is determined by X-ray crystallography. In addition, the di s te th e sity of the coupling shows a dependence of temperature favoring the R-isomer at room temperature with a 50% ternary excess. At low temperature the selectivity is inverted, favoring the S isomer with more or less the same excess ter ter ér ico (Table 1) To make both isomers available the coupling is carried out at 0o provided both diastereomers in combined yield of 92 - 96 .

S-3 R-3 Table 1. Dependence of the di e ro s e 1 ec tivity of the copper coupling mediated on the temperature The disconcerting feature of these new compounds R-3 and S-3 is that they behave as true enatiomers in any type of asymmetric reactions despite their erieeric nature. This is shown first by testing the set of bistosteroids 3-5 in enanti-reductions and acetyphenone acetylides following the Noyori protocol (J. Chem. Soc. 1979, 101, 3129); (Table 2).

R-4 R-5 Table 2. Reductions in acetofenone reagents induced by ligands b is e s t e r ide ides. a) determined by GC The result in Table 2 shows that the new bi s e te rs ides are powerful as reduction agents to be carried out at -90 ° C as in the Noyori protocol. With ligand 4, which is completely soluble at -90 ° C, the same enantiomeric excesses in acetophenone reduction are achieved as Noyori. The absolute configuration of the reduction products is also the same as in the Noyori reduction. The reduction of the two R and 3 S-3 ionic ligands produces the opposite enantiomers of the reaction product. The R- / S-4 and R- / S-5 eroids were prepared by mediated copper coupling (Tetrahedron 1992, 48, 2579) of 4-b rorno-17 ß-me t o x i -3-methoxymethoxyestra-l, 3, 5 (10) -triene (Tetrahedron 1991, 47, 2871) 11 and 4 -brorno - 3 -me t ox iet oxestr a-1, 3, 5 (10) -trieno 14. In addition, the ligand di ertico rs R-3 and S- 3 are incorporated in the catalysis of chiral titanium R-Ti-1 and S-Ti-1 (Tetrahedron Lett, 1991, 32, 6271).

These catalysts were then used as Lewis chiral acids for the enant ioselect i va cyclization of Methylsecona, yielding 3-methoxyestra-1, 3,5 (10), 8, 14-pentaen-17-one in, notably high yield and excess enant iomer i co (Table 3).

R-Ti-1 X = BF S-Ti-1 X = BF4 Table 3. Cyclization elective enantios of methyl-sesame with R-Ti-1 and S-Ti-1.

More interestingly, the catalysts R-Ti-1 and S-Ti-1 offer the product 3-methoxyestra- 1, 3, 5 (10), 8, 14 -pent aen-17 -one due to its tereomeric nature with a different chemical and optical performance each. The synthesis of (Ra) - and (Sa) -4,4 '-bi s (3-trifluoromethylsulfonyloxiestra-1, 3, 5 (10), 6, 8 -pentane) 6 was completed by filtration of R- / S- 3 with triflic acid anhydride in the presence of pyridine in quantitative yield.

R- / S-3 R- / S-6 The trifalt 6 was then converted to bisphosphine 7 without any isomerization of the diastereomers in 83% yield.

R- / S-6 R- / S-7 Starting with Equilinin 1 both bisphosphines R-7 and S-7 are available in 4 chemical stages in an overall yield of 64%. The epimeric phosphines Epi-R-7 and Epi-S-7 are available according to a similar synthetic sequence initiating with Epi-equi 1 in ina 14-Epi-1 (Tetrahedron Lett 1971, 4179). 14-epi-1 14-epi-R- / S-6 14-epi-R- / S-6 14-epi-R- / S-7 The new R-7 and S-7 phosphines were tested as chiral ligands in a ruthenium complex for the asymmetric hydrogen acetoacetate methyl, N-ac eti 1-conamic acid and tiglic acid as representative examples (Table 3). The chiral ruthenium complex is prepared by heating the R- / S-7 bisphosphines with [RuCl2 (benzene)] 2 in DMF (Tetrahedron Lett, 1991, 32, 4163). Table 3. Asymmetric hydrochloride of methyl acetoacetate and N- a ce t i 1 - cinámi co acid * lh / 100atm / 100 ° C; ** 48h / 7atm; *** 24h / 4atm; **** 96h / 7 atm; The new chiral complexes synthesized from [RuCl2 (benzene)] _ and ligands biseste ro i dal is 7 more potent than those manifested by the complex technique of BINAP-ruthenium from Nayori as being of wide applicability and allow the preparation of a variety of substrates of high purity enant i orne ri ca extraordinary in a quantitative yield. In addition, the new ligands biseste ro i da 1 is 3-5 have proven to be highly effective for the reduction in ketone readings exemplified by the reduction of acetophenone and are chiral Lewis acids highly effective and cyclized by cyclization. enant io sel ecti va de me ti 1-s econa.

Examples Preparations Optical rotations are measured in a polarimeter Per in El er 241, the melting points are not correct; the spectrum 'H NMR (300 MHz), and 13C-NMR (75MHz) are taken over General Electric QE 300 in CDC13 as a solvent and internal reference (7.28 ppm, 81.9 ppm); the J values are given in Hz; the IR spectrum was taken on Nicolet 20 SBX; the mass spectrum is recorded on TRIO "; TLC is performed on Merck 60 F 254. Silica gel 60G (240-400 mesh) is used for column chromatography All reactions are carried out under nitrogen or dry argon. 1. Synthesis of the R- / S-7 phosphines: 1. A suspension of 53.15 g of 3-hydroxy-1, 3, 5 (10) 6, 8-estr apent aen-17 -one 1 (0.199 mmoles) in 36.3 ml of hydrazine hydrate, 435 ml di eti 1 engl icol and 36.5 g of NaOH (0.91 moles) are heated in an oil bath at 120 ° C. After stirring at this temperature for 0.5 hours, the temperature is increased to 180 ° C and stirred for an additional 8 hours. After cooling to room temperature, the solution is added to 500 ml of ice water and then acidified with concentrated HCl to pH 0. The precipitate is filtered off, dried and the unpurified product recrystallized from water -ethanol 1: 1 (100 ml each) giving 42.7 g of Es tr a- 1, 3, 5 (10) 6, 8-pentaen-3-ol 2 (85%); mp = 136.5 ° -139 ° C; [a] ,, - = + 228.7o (c = 10.2 in THF). 2. To a solution of Estra-1, 3,5 (10) 6,8-pentaen-3-ol 2 (10Og, 20 mmol) in CH ~ C12 (300 ml) is added CuC 1 (OH) • TMEDA ( 0.800 g, 0.35 mmol) and the solution is stirred at 0 ° C for 10-15 minutes while bubbling oxygen through the mixture. The reaction is monitored by TLC. At the end of the reaction, HCl (10%, 5 ml) is added to the mixture and stirred for an additional 15 minutes (the color changes from blue to yellow). The mixture is filtered and the residue is dried under vacuum to give the product without purification (5 g). From the filtrate after extraction with CH2C12 (3 x 10 ml), 4.8 g of the product is additionally isolated which is combined with the first fraction. The crude mixture is separated to give 5.9 g (Ra) -4,4'-bis (estra-1, 3, 5 (10) 6, 8-pentaen-3-ol) 3 (59%) as the main isomer; p. f. 207, 4-207, 5 ° C; [a] 36s = + 303.13 ° (c = 1.6 in THF); ^ -RMN: 8.15 (1H, d, J = 10.0Hz), 7.38 (1H, d, J = 10.0Hz), 7.09 (1H, d, J = 7.5Hz), 7.01 (1H, d, J = 7.5 Hz), 4.98 (1H, s, OH), 0.70 (3H, s); 'C-NMR: 151.3 (s), 135.2 (s), 131.8 (s), 130, 9 (s) 126. 6 (s), 126.5 (d), 126. l (d), 122.0 (d), 116.8 (d), 111. 7 (s), 49.7 (d), 40.4 (s), 38.7 (t), 35.8 (t), . 2 (t), 24.7 (t), 20.9 (t), 16.2 (c); MS-C1: 520 (100, M '+ 1 + NH 3), 503 (90 M +); MS-E1: 502 (100, M +), 389 (5), 235 _ (10), 195 (5) 157 (7); and 3.7 g of (Sa) -4,4 '-bi s (E s t ra- 1, 3, 5 (10) 6, 8 -pent aen-3-or 1) 3 secondary isomer (37%), p. f. 287.0 ° C decomposition (Hexane); [a] = + 145.18 ° (c = 1.4 in THF): H-NMR: 8.10 (1H, d, J = 9.0 Hz), 7.32 (1H, d, J = 9.0 Hz), 7.05 (1H, d, J = 6.0 Hz), 6.98 (1H, d, J = 6.0 Hz), 5.10 (1H , s, OH), 0.70 (3H, s); 13 C-NMR: 151.3 (s), 135. l (s), 131.6 (s), 130.9 (s), 127.6 (s), 126.5 (d), 126. l (d), 121.8 (d), 116.8 (s) d), 111.7 (s), 49.7 (d), 40.4 (s), 38. 7 (t), 35.8 (t), 25.2 (t), 24.7 (t), 20.9 (t), 16.2 (c); MS-C1: 520 (88, M + + 1 + NH3), 503 (100, M "); MS-E1: 502 (100, M +), 389 (5), 251 (6), 235 (10), 195 (5), 157 (7); 3. To a solution of (Sa) -4,4 '-bis (Estra-1, 3, 5 (10) 6, 8-pentaen-3-ol) 3 (1.8 g , 3.6 mmol) in toluene-pir idine 15: 1 (30 ml) is added dropwise over a period of 30 minutes trilic anhydride and the mixture is stirred for an additional 30 minutes.The solution is diluted with water, the organic layer is washed with brine, dried with Na 2 SO 4 and the solvent was evaporated The residue was filtered through SiO 2 to produce the crude product (2.8 g) which, after crystallization from hexane, gave 2.5 g of pure triflate (S). a) - 4,4'-bis (3-trifluoromethylsulfonyloxiestra-1, 3, 5 (10), 6, 8 -pentane) 6 (901), p.f. = + 168.2 ° C; [a] D = - 97.6 ° (c = 1.7 in THF), XH-NMR: 8.25 (1H, d, J = 10.0 Hz), 7.58 (1H, d, J = 10.0 Hz), 7.12 (1H, d, J = 9.0 Hz), 7.01 (1H, d, J = 9.0 Hz), 0.65 (3H, s); 13C-NMR: 144.3 (s), 138.5 (s), 131.6 (s), 130.9 (s) , 130.7 (s), 126.9 (d), 126.6 (d), 124.3 (d), 123.5 (s), 118.2 (d), 49.9 (d), 40.3 (s), 38.6 (t), 35.6 (t) , 24.9 (t), 24.7 (t), 20.8 (t), 16.2 (c); 19F-NMR: 87.12; MS-C1: 784 (3, M * + 1+ NH., MS-EI: 766 (100, M +), 633 (7) 483 (85), 389 (6), 309 (7), (Ra) - 4, '-bis (3-Trif luoromethylsulfonyloxiestra-1, 3, 5 (10), 6, 8 -pent aeno) 6: The compound is synthesized according to the same procedure as (Sa) -4,4'-bis ( 3-Trifluoromethylsulfonyloxiestra-1, 3, 5 (10), 6, 8-penta-ene) 6 to give after recrystallization the pure compound, p.f. = 201.9 ° C. [A] D = -88.2 ° ( c = 1.0 in THF), XH-NMR: 8.25 (1H, d, J = 10.0 Hz), 7.59 (1H, d, J = 10.0 Hz), 7.12 (1H, d, J = 9.0 Hz), 7.01 (1H , d, J = 9.0 Hz), 0.66 (3H, s); 13 C-NMR: 144.3 (s), 138.5 (s), 131.6 (s), 131.0 (s), 130.7 (s), 126.9 (d), 126.8 (d), 124.3 (d), 123.5 (s), 118.2 (d), 49.9 (d), 40.3 (s), 38.6 (t), 35.6 (t), 24.9 (t), 24.7 (t), 20.8 (t), 16. 2 Ce); 19F-NMR: 87.12; MS-CI: 784 (8, M ++ l + NH 3), MS-EI: 766 (100, M +), 633 (7) 483 (75), 389 (6), 309 (7), 4. To a solution of NiCl2dppe (0.070 g, 0.13 mmol) in dimethyl acetamide (2 ml ) is added di f eni 1 fo sf ina (0.13 ml, 0.75 mmole) at room temperature, and the solution is heated to 100 ° C. After 45 minutes, a solution of triflate (Ra) - or (Sa) -4,4 '-bis (3-Trifluoromethylsulfonyloxiestra-l, 3, 5 (10), 6, 8-pentaeno) (lg, 1.3mmoles) ) and then add 1, 4-di az ab i ci cl or [2.2.2] oct anus (0.62 g, 5.5 mmol) in dimethyl acetamide (4 ml), the resulting green solution is maintained at 100 ° C and three additional portions of di f eni 1 phosphine (3 X 0.13 ml) are added at, 3 and 5 h later. The reaction is maintained at 100 ° C for six days and then the dark brown solution is diluted with MeOH. The desired product is filtered and the filter cake washed with MeOH and dried under vacuum. The crude product (0.820 g, 80S) is recrystallized from 10: 1 MeOH / Tol to give 0.78 g of pure phosphine (Ra) -4,4'-bis (3-diphenylphosphinoestra-1, 3, 5 (10)). ), 6, 8-pentane) 7: (70 ?,), XH-NMR: 8.05 (1H, d, J = 10.0 Hz), 7.42 (1H, broad, J = 10.0 Hz), 7.3-6.9 (10H, m) 6.50 (2H, ABq, J = 8.0 Hz), 3.30 (2H, broad, J = 8.5Hz), 2.63 (1H, dd, J = 5.1, 11.0 Hz), 2.2-1.3 (7H, m), 0.70 (3H, s); 13 C-NMR: 145.8 (s), 138.8 (s), 137.4 (s), 133.6 (s), 132.6 (s), 131.6 (s), 130. 6 (s), 130.1 128.3, 128.2, 127.6, 125.7, 124.9, 123. 3, 50.3 (d), (each d), 40.7 (s), 39.0 (t), 36.1 (t), 25.4 (t), 24.9 (t), 21.2 (t), 16.8 (c); "- P-NMR: 15.42 (s); MS-C1: 784 (8, M '+ 1 + NH'), MS-EI: 766 (100, M +), 633 (7) 483 (75), 389 ( 6), 309 (7), (Sa) - 4, 4 '-bis (3-Dif enylphosph inoestra-1, 3, 5 (10), 6, 8-pentaene) 7: (70%), [a] D = -97.6 ° (c = 0.17 in THF), XH-NMR: 7.92 (1H, d, J = 10.0 Hz), 7.39 (1H, broad, J = 10.0 Hz), 7.3-6.9 (10H, m), 6.75 (2H, ABq, J = 8.0 Hz), 3.38 (1H, dd, 5.6, 21.0 Hz), 3.22 (1H, m), 2.72 (1H, dd, 6.5, 11.6 Hz), 2.12 (2H, m), 1.9-1.3 (5H, m), 0.55 (3H, s); 13C-NMR: 146.2 (s), 137.6 (s), 133. 5 (s), 133.1 (s), 132.5 (s), 131.8 (s) 131.5 (s), 130.0 (d), 129.9 (s), 127.6, 127.5, 126.9, 125.5, 124.8, 122.9 50.0 (each d), 40.3 (s), 38.7 (t), 35.8 (t), 25.0 (t) , 24.6 (t), 20.8 (t), 16.4 (c); 31 P-NMR: -14.42 (s); MS-C1: 784 (8, M * + 1 + NH 3), MS-EI: 766 (100, M +), 633 (7) 483 (75), 389 (6), 309 (7). 2. Synthesis of the Epi-R- / S-7 phosphines: 1. To a suspension of 14 -Ep i - 3 -hi dr ox i -1, 3, 5 (10) 6, 8 - stringent 17 14-Epi-lone (10 g, 38 mmol) in CH2C12 (300 mL) is added CuCI (OH) TMEDA (0.800 g, 0.35 mmol) and the solution is stirred at 0 ° C for 10-15 minutes while bubbles oxygen through the mixture. The reaction is monitored by TLC. At the end of the reaction, HCl (10 =, 5 ml) is added to the mixture and stirred for an additional 15 minutes (the color changes from blue to yellow). The organic layer is washed with brine, dried and the solvent is evaporated. The crude mixture (9.9 g) is separated to give 5.2 g of (Ra) -4,4 '-bis (14 -Ep i-3-h idroxy -1, 3, 5 (10) 6, 8-estrapentaen- 17-one) (52%); p.f. 293 ° C decomposition; [a] 365 = + 139.5 ° '(c = 2.4 in THF); 'H-NMR: 8.17 (1H, d, J = 9.3 Hz), 7.38 (1H, d, J = 9.3 Hz), 7.07 (1H, d, J = 8.5 Hz), 6.98 (1H, d, J = 8.5 Hz), 4.85 (1H, s, OH), 1.50 (3H, s); MS-CI: 520 (100, M "+ 1 + NH3), 503 (90, M +); MS-EI: 530 (100, NT), 474 (15), 209 (20), 181 (25), 165 (twenty); and 4.3 g (Sa) -4,4 '-bis (14 -Ep i-3 -hi dr oxy -1, 3, 5 (10) 6, 8-estrapentaen-17-one) (43%), m.p. 180 ° C decomposition. (Hexane); [a] 30 ^ = + 154.0 ° (c = 2.0 in THF); ^ -RMN: 8.15 (1H, d, J = 9.3 Hz), 7.42 (1H, d, J = 9.3 Hz), 7.15 (1H, d, J = 8.6 Hz), 7.05 (1H, d, J = 8.6 Hz), 4.98 (1H, s, OH), 1.19 (3H, s); MS-CI: 520 (88, M "+ 1 + NH 3), 503 (100, M"); MS-EI: 530 (100, M ^), 474 (15), 209 (36), 181 (38), 165 (40); 2. To a solution of (S a) -4,4 '-bis (14 -Ep i-3-hydroxy- 1, 3, 5 (10) 6, 8 -est rapent aen-17 -ona) (2.2 g, 4.2 mmoles) and N-ethi Idi i sop rop i 1 ai na (4 ml, 23 mmol) in toluene (60 ml) is added dropwise over a period of 30 minutes to triflic anhydride (3.6 ml, 10 mmol). The mixture is stirred for 30 minutes at room temperature and then heated to 60 ° C and maintained at this temperature for 3 hours. At the end of the reaction the mixture is cooled and the top layer (toluene) is separated and washed with water, 2N HCl and brine, dried with Na, SO¿ and the solvent evaporates. The residue is dissolved in ethanol (30 ml) and exposed to hydrogen (1 at) in the presence of Pt02 (0.2 g) during 2h. The mixture is filtered through a pad of celite, the solvent is evaporated and the unpurified product is dissolved in ethyl acetate. The solution is washed with NaHCO 3, brine and dried with Na? S04. The solvent is evaporated and the unpurified product is separated over SiO2 to produce (Sa) -4,4 '-bis (14-Epi-3-trifluoromethylsulfonyloxy-es-ra-1, 3, 5 (10), 6, 8-pentaeno) 14-Epi-S-6 (2.6 g) (86-,), mp = 115-116 ° C; [a] D = + 128.8 ° (c = 0.1 in THF), : H-NMR: 8.28 (1H, d, J = 10.0 Hz), 7.60 (1H, d, J = 10.0 Hz), 7.12 (1H, d, J = 9.0 Hz), 6.98 (1H, d, J = 9.0 Hz), 1.10 (3H, s); 13 C-NMR: 144.8 (s), 139.2 (s), 132.0 (s), 131.4 (s), 130.7 (d), 130.4 (s), 126.6 (d), 124.5 (d), 120.3 (s), 118.5 (d), 50.7 (d), 40.7 (t), 39.3 (s), 35.4 (t), 31.4 (t), 25.7 (c), 23.2 (t), 22.7 (t); MS-CI: 784 (100, M ++ 1 + NH 3), S-EI: 766 (80, M +), 633 (17) 483 (100), 387 (21), 308 (17), (Ra) - 4, 4 '-bis (14-Epi-3-trif luoromethylsulfo-nyloxiestra-1, 3, 5 (10), 6, 8-pentaene) 14-Epi-R-6: The compound is synthesized according to the same procedure as (S a) -, 4 '-bi s (14-Epi-3-trifluoromethylsulfonyloxiestra-1, 3, 5 (10), 6, 8-penta-ene) 14-Epi-S-6 to give after the recrystallization of the pure compound; p.f. = 204-204.5 ° C, [a]: = - 23.9 ° (c = 0.1 in THF), XH-NMR: 8.28 (1H, d, J = 10.0 Hz), 7.60 (1H, d, J = 10.0 Hz) , 7.11 (1H, d, J = 9.0 Hz), 7.01 (1H, d, J = 9.0 Hz), 1.10 (3H, s); 'C-NMR: 144.3 (s), 139.2 (s), 132.0 (s), 131.4 (s), 130.8 (d), 130.5 (s), 127.0 (d), 124.6 (d), 124.9 (s), 118.5 (d), 50.6 (d), 40.6 (t), 39.6 (s) 35.4 (t), 31.5 (t), 25.7 (c), 23.3 (t), 22.8 (t), MS-CI: 784 ( 88, M ++ 1 + NH 3), MS-EI: 766 (100, M +), 633 (17) 483 (75), 389 (26), 309 (7), 3. To a solution of NiCl 2dppe (0.070 g, 0.13 mmoles) in dimethyl acetamide (2 ml) is added to the ice (0.13 ml, 0.75 mmole) at room temperature, and the solution is heated to 100 ° C. After 45 minutes, a solution of triflate (Ra) - or (Sa) -4,4 '-bis (14-Epi-3-trif luoromethylsulfonyloxy-estra-l, 3,5 (10), 6, 8-pentaeno) (lg, 1.3 or les) and then 1 is added, 4 -di az ab i c it [2.2.2] oc t (0.62 g, 5.5 mmol) in dimethyl acetamide (4 ml), the resulting green solution is maintained at 100 ° C and three additional portions of di f eni 1 phosphine (3 X 0.13 ml) are added at, 3 and 5 h after. The reaction is maintained at 100 ° C for six days and then the dark brown solution is diluted with MeOH. The desired product is filtered and the filter cake is washed with MeOH and dried under vacuum. The crude product (0.820 g, 80%) is recrystallized from 10: 1 MeOH / Tol to give 0.78 g of pure phosphine. (Sa) -4,4 '-bis (14-Epi-3-diphenylphosphinoestra-1, 3, 5 (10), 6, 8-pentaeno) 14-Epi-7: (89%), [a] D = -79.3 ° (c = 0.13 in THF),: H-NMR: 7.98 (1H, d, J = 10.0 Hz), 7.36 (1H, broad d, J = 10.0 Hz), 7.3-6.9 (10H, m), 6.52 (2H, s), 3.12 (1H, dt, 3.2, 21.0 Hz), 2.95 (1H, m), 2.52 (1H, t, 7.5 Hz), 2.1 (2H, m), 1.7 (1H, m), 1.9-1.3 (5H,), 0.98 (3H, s); 'C-NMR: 146.4 (s), 146.0 (s), 138.2 (s), 133.1 (s), 132.8 (s), 132.0 (s) 129.5 (s), 129.9 (s), 130.3 128.8, 128.3, 127.9 , 127.4, 125.6, 123.2 50.0 (each d), 40.3 (s), 38.7 (t), 35.8 (t), 25.0 (t), 24.6 (t), 20.8 (t), 16.4 (c); 31 P-NMR: -15.2 (s); 3. Synthesis of (Ra) -bis (17 be t a-Me t oxi estr a-1, 3, 5 (10) -trien-3-ol) 4 and (Ra) -4, 4 '-bis (Estra -1, 3, 5 (10) -trien-3-ol) 5 R - OH: 10 U L7 R - OMß: IX X - OM «.m 3-12 X - OMa.Hl R-12 X ~ OHß, H: R-12 X-OMß.H: R-4 X-H, H: R-15 X-H.H: R-5 3. 1 Synthesis of (Ra) -bis (17 beta-methoxystra-1, 3, 5 (10) -trien-3-ol) 4: 1. A solution of 4-Bromo-3-hydroxyl is tr a-1 , 3, 5 (10) -thien-17 -one 8 (20 g, 51 mmol) in dimethyl formamide (250 ml) is added t-BuOK (7.7 g, 74 mmol) at 0 ° C. The mixture is stirred for 5 minutes and then a solution of methoxymethyl chloride (5.5 g, 68 mmol) in dimethyl formamide (15 ml) is added dropwise at the same temperature and stirred for an additional 1 h. The reaction is quenched with saturated NH 4 Cl and diluted with water (130 ml). The crude product is filtered and recrystallized from ethanol to give 21.5 g of 4 -Br orno-3-methylperoxymethyl estr a- 1, 3, 5 (10) -trien-17-one 9 pure (95.5% ), pf 172 °; 2. 4-Bromo-3-methoxymethoxystra-l, 3, 5 (10) -trien-17-one 9 (20 g) is reduced with 10.6 g of NaBH 4 (15 mmol) in 300 ml of methanol to give alcohol 4 -Bromo-3-methoxymethoxystra-l, 3, 5 (10) -trien-17-beta-ol-10 (20 g) which was used without purification for the next step. 3. To a solution of 4-Bromo-3-metoximetoxy is tra- 1, 3, 5 (10) -trien- 17 beta-ol. (20 g, 50 mmol) in DMF (250 ml) is added t-BuOK (7.9 g, 75 mmol) at 0 ° C. The mixture is stirred during minutes and then a solution of MeJ (9.2 g, 65 mmol) in dimethyl formamide (15 ml) is added dropwise at the same temperature and stirred for an additional 15 h. The reaction is quenched with saturated NH4CI and diluted with water (130 ml). The crude product is filtered and recrystallized from ethanol to yield 19.7 g of 4-Bromo-17-beta-methoxy-3-methoxymethoxystra-l, 3, 5 (10) -trien. (941); [a] 365 = + 49, 6 ° (c = l in THF); XH-NMR: 7.18 (1H, d, J = 9.0 Hz), 6.95 (1H, d, J = 9.0 Hz), 5.22 (2H, s), 3.52 (3H, s), 3.48 (3H, s), 3.30 (1H, t, J = 7.5 Hz), 2.98 (1H, dd, J = 5.8, 19.5 Hz), 2.70 (1H, m), 0.75 (3 H, s); 13C-NMR: 151.3 (s), 137.3 (s), 135.8 (s), 124. 4 (d), 115.9 (s), 113.0 (d), 94.9 (t), 90.4 (d), 57. 4 (d), 55.9 (s), 49.9 (d), 43.8 (d), 42.8 (s), 37.6 (t), 37.4 (d), 30.8 (t), 27.4 (t), 27.1 (t), 26. 3 (t), ~ 22.7 (t), 11.1 (c); Calculated Analysis (C.:H_;.03Br) C-61.75, H-7.16, 0-11.76, Br-19.52; Found: C-60.95, H-7.80, 0-11.72, Br-19.60. 4. To a solution of 4 -Br orno- 17 -be t a-me t oxy -3 -metoxime toxi e s t r a- 1, 3, 5 (10) -t r i in 11 (10 g, 24. 4 mmoles) in THF (250 ml) is added BuLi (16 ml, 1.6 M, 26 mmoles) at -60 ° C. The mixture is stirred for 30 minutes and then a suspension of CuCN (1.1 g, 12 mmol) in THF (25 ml) is added at the same temperature. Stirring is continued for an additional 2.5 h until the CuCN is not visible at the bottom of the flask. After cooling to -100 ° C, dry oxygen is passed through the mixture for 15 minutes which results in an intense purple color. The oxygen flow is switched off and the reaction mixture is stirred for an additional 30 minutes at this temperature and then quenched with saturated NH 4 Cl and diluted with diethyl ether (100 ml). The organic layer is washed with brine, dried with Na 2 SO 4 and the solvent is evaporated. The crude mixture (7.8 g) is crystallized from 8: 1 e t i 1-hexane acetate. The solid product is filtered and dried to give 2.9 g of the isomer (Ra) -4,4'-bis (17 -be t-Me-tox-3 -me tox ie toxie str- 1, 3, 5 ( 10) - tri eno) 12 pure (36%). The filtrate is evaporated and the residue is separated by chromatography on SiO2 (he ano: di eti 1 é t er- 6: 1) to give the additional product (0.2 g, 2%) which is combined with a first one and used without further purification. XH-NMR (unpurified): 7.28 (1H, d, J = 9.0 Hz), 7.05 (1H, d, J = 9.0 Hz), 5.09 (1H, d, J = 6.0 Hz), 4.95 (1H, d, J = 6.0 Hz), 3.48 (3H, s,), 3.30 (1H, t, J = 8.5 Hz), 3.30 (3H, s), 0.80 (3H, s); l3C-NMR: 151.7 (s), 136.1 (s), 134.1 (s), 126.3 (s), 124.6 (d), 111.9 (d), 94.2 (t), 81.5 (d), 55.2 (d), 52.9 (s), 50.0 (d), 44.0 (d), 42.9 (t), 37.9 (d), 36.5 (t), 30.3 (t), "26.9 (t), 25.9 (t), 22.7 (t), 16.2 (c): 5. To a solution of (Ra) -4,4 '-bis (17-beta-methoxy-3-methoxy e toxiestra-1, 3, 5 (10) -triene) 12 (2 g, 3 mmol) in MeOH / THF / H20 1: 1: 0.2 (20 ml) concentrated HCl (3 ml) is added, the mixture is stirred for 25 h at room temperature, the reaction mixture is neutralized with saturated NaHCO 3 and diluted with ethyl ether (50 ml) The organic layer is washed with brine, dried over Na 2 SO 4 and the solvent is evaporated The crude product (1.3 g, 78%) is recrystallized from Hexane ethyl ether 1: 1 to give 1.1 g of (Ra) -bi s (17 -be t a -Me tox iestr a- 1, 3, 5 (10) -trien-3-ol) 4 (70%), mp 181 ° C, [a] j. = -96.30 ° (c = 1.54 in THF); XH-NMR: 7.25 (1H, d, J = 10.0 Hz), 6.82 (1H, d, J = 10.0 Hz), 4.72 (1H, s, OH), 3.38 (3H, s), 3.32 (1H, t, J = 7.5 Hz), 0.80 (3H, s); 13C-NMR: 150.7 (s), 136.6 (s), 133.3 (s), 126.8 (d), 124.6 (s), 112.9 (d), 90.4 (d), 57.5 (d), 50.0 (s), 43.8 (d), 42.8 (t), 37.8 (d), 37.6 (t), 27.3 (t), 26.9 (t), 26.7 (t), 22.6 (t), 11.2 (c); Analysis. Calculated (CJ &Heo04) C-79.96, H-8.83, Found: C-79.46, H-7.90. 3.2 Synthesis of (Ra) -4,4 '-bis (Estra-1, 3, 5 (10) -trien-3-ol) 5: 1. To a solution of 4 -Brine-3 -hydr ox i -es After 1, 3, 5 (10) -triene (20 g, 60 mmol) in dimethylformamide (250 ml), t-BuOK (9.3 g, 89 mmol) was added at 0 ° C. The mixture is stirred for 5 minutes and then a solution of methoxymethyl chloride (6.3 g, 78 mmol) in DMF (15 ml) is added dropwise at the same temperature and stirred for an additional 1 h. The reaction is quenched with saturated NH4C1 and diluted with water (130 ml). The crude product is filtered and recrystallized from ethanol to give 20.4 g 4- Bromo-3-methoxymethoxy-estra-l, 3,5 (10) -triene 14 (90 '); p.f. 85.2 ° C, [a] D = + 50.8 ° (c = l in THF); : H-NMR: 7.22 (1H, d, J = 9.0 Hz), 6.97 (1H, d, J = 9.0 Hz), 5.22 (2H, s,), 3.55 (3H, s,), 0.72 (3H, s ); 13 C-NMR: 151.3 (s), 135.2 (s), 131.8 (s), 130.9 (s), 127.6 (s), 126.5 (d), 94.2 (t), 81.5 (d), 55.2 (d), 52.9 (s), 50.0 (d), 44.0 (d), 42.9 (t), 37.9 (d), 36.5 (t), 30.3 (t), 26.9 (t), 25.9 (t), 22.7 (t), 16.2 (c); MS-CI: 398, 396 (100, M "+1 + NH3); MS-EI: 380, 378 (30, M +), 350, 348 (25), 251 (6), 173 (10); Calculated Analysis (C20H27? 2Br) C-63.33, H-7.17, 0- 8.44, Br-21.06; Found: C-63.28, H-7.20, Br-21.00; 2. To a solution of 4 -Br orno- 3 -me t oxime t ox i -estra-1, 3, 5 (10) -triene 14 (12 g, 31.7 mmoles) in THF (250 ml) is added BuLi (24 ml, 1.6 M, 38 mmoles) at -60 ° C. The mixture is stirred for 30 minutes and then a suspension of CuCN (1.5 g, 17 mmol) in THF (25 ml) is added at the same temperature. The mixture is stirred for an additional 2.5 h until CuCN is not visible at the bottom of the flask. After cooling to -100 °, dry oxygen is passed through the mixture for 15 minutes. The oxygen flow is switched off and the reaction mixture is stirred for an additional 30 minutes at this temperature and then quenched with saturated NH C1 and diluted with diethyl ether (100 ml). The organic layer is washed with brine, dried with NaSO: and the solvent is evaporated. The residue (10 g) is dissolved in DMF (30 ml) and added to the t-BuOK solution (1.9 g, 18 mmol) at 0 ° C. The mixture is stirred for 5 minutes and then a solution of TBDMSCI (2.5 g, 65 mmol) in DMF (15 ml) is added at the same temperature and stirred for an additional 30 minutes. The reaction is quenched with saturated NH_C1 and diluted with ethyl ether (50 ml). The organic layer is washed with brine, dried with Na 2 SO 4 and the solvent is evaporated. The crude mixture (11 g) is separated by chromatography on SiO, (hexane: die ti lé t er-6: 1) to give 2 g of the crystalline product (Ra) -4,4'-bis (3-methoxymethoxystra- 1, 3, 5 (10) -triene) 15 (21%) which is used without purification for the next stage. 3. To a solution of (Ra) -4,4 'bis (3-Me toxime tox iestr a- 1, 3, 5 (10) -triol) 15 (2 g, 3.3 mmol) in Method 1 / THF / H20 1: 1: 0.2 (20 mL) is added concentrated HCl (3 mL) and stirred for 25 h at room temperature. The reaction mixture is neutralized with. NaHC03 saturated and diluted with ethyl ether (50 ml). The organic layer is washed with brine, dried with Na 2 SO 4 and the solvent is evaporated. The crude product (1.3 g, 78%) is recrystallized from hexane / et illite 1: 1 to give 1.3 g (Ra) -4,4 '-bis (Estra-1, 3, 5 ) -trien-3-ol) 5. { 16%), p.f. 162.5 ° C, [a] j85 = -96.30 ° (c = 1.54 in THF); ^ -RMN: 7.25 (1H, d, J = 10.0 Hz), 6.82 (1H, d, J = 10.0 Hz), 4.72 (1H, s broad OH), 0.72 (3H, s); : JC-NMR: 150.8 (s), 136.7 (s), 133.6 (s), 126.8 (d), 111.8 (s), 112.3 (d), 53.3 (d), 43.9 (d), 40.7 (s), 40.2 (t), 38.5 (t), 38.3 (d), 27.6 (t), 27.1 (t), 26.4 (t), 24.8 (t), 20.2 (t), 14.8 (c); MS-CI: 520 (100, M ++ 1 + NH 3), 503 (92, M + + 1); MS-EI: 520 (100, M +), 251 (4), 235 (6); Calculated Analysis. (C36H4b02) C-84.66, H-9.08, Found: C-84.94 H-9.12, 0-6.20.

Examples of applications: 1. Reduction of acetophenone with the R-4 ligand: A dry 50 ml Schlenk tube containing a Teflon-coated stir bar is charged with a solution of LiAlH in THF (1.5 ml, 0.98 M) and then a solution of, ethyl alcohol in THF (0.9 ml, 1.7 M) is added dropwise over a period of ca. 10 minutes. Subsequently a THF solution of R-4 (3 ml, 0.53 M). it is added by dripping during a period of 30 minutes. After stirring for an additional 30 minutes at room temperature the reducing agent is cooled to -90 ° C. A solution of acetophenone (0.45 ml, 0.7 M) in THF (over a period of 20 minutes) is slowly added. The mixture is stirred for an additional 3 h at this temperature and at -78 ° C for 16 h. After the addition of methanol (0.5 ml) at -78 ° C the mixture is heated above room temperature, neutralized to pH = 6 with HCl (5%) and extracted with ethyl ether (2 X 10 ml). GC analysis (25 _ m FS-Hydrodex-B-PM, 110 isotherm, 1 bar Hydrogen, tect or t = 280 ° C, t ° column = 280 ° C) of the extracts shown 96.5% ee and conversion comp 1 eta 2. Hydrogenation of olefins and b-C e t oes t e r e s and with ligand R-4: A dry 50 ml Schienk tube containing a stir bar coated with Teflon is charged with [RuCl2 (benzene)] 2 (0.018 g, 0.036 mmol), S-4 (0.07 g, 0.073 mmol) and DMF (1 ml). The resulting brown suspension is heated at 1 ° C under argon for 30 minutes to give a clear reddish-brown solution. The reaction mixture is cooled and concentrated to 1 mu Hg and then to 0.05 mm Hg for 1 h to give RuCl, (S-4) (DMF). a) Hydrogenation of methyl acetoacetate To the reddish brown solid resulting from RuCl (S-4) (DMF) 2 a solution of methyl acetoacetate (7.3 g, 63 mmol) in degassed methanol (40 ml) is added and stirred for 5 minutes. The solution is then transferred to 125 ml stainless steel autoclave and kept at 100 ° C and under hydrogen (100 atm) and then 10 h at room temperature and at the same pressure. After the excess hydrogen has been blown, the apparatus is disassembled. The content is concentrated. Distillation (110 ° C, 46 m Hg) provides methyl (S) -3-hydroxybutanoate (7.22 g, 98 [a] - = -50.5 c = 1.4, [a] 546 = -58.3 c = 1.4 in CHC13) , in 99% ee analyzed as MTPA ester. b) Hydrogenation of acrylic acid: To the reddish-brown solid resulting from RuCl (S-4) (DMF) 2 a solution of a-acetamidocinnamic acid (3.6 g, 17 mmol) in degassed methanol (40 ml) is added and Stir for 5 minutes. Then the solution is transferred to 125 ml stainless steel autoclave and kept 48h at room temperature and under hydrogen (4 atm). After the excess hydrogen has been blown, the apparatus is disassembled. The content is concentrated to give 3.6 g of the product without purification. A similar amount of the unpurified product (0.05 g) is treated with excess diazomethane (ethyl ether solution) to produce the corresponding methyl ester for the determination of the enantomeric excess. GC analysis (25 m Chi raisi 1 -DEX, 150 ° isotherm, 1 bar hydrogen, detector t = 280 ° C, t ° co lumn = 280 ° C) of these esters shown in ee of 85.7% and signal of the initial material . The rest of the product is dissolved in hot water (200 ml) and extracted with toluene (2X30 ml). The water is evaporated and the residue is dried under vacuum to give to give 3.48 g (96%) (-) - N-acetyl-phenyl alanine, [a] D = -33.7 (c = 1.0 in methanol). c) Hydrogenation of Tíglico acid: To the reddish brown solid resulting from RuCl. (S-4) (DMF) 2 a solution of tíglico acid is added (1.2 g, 17 mmol) in degassed methanol (30 ml) and stirred for 5 minutes. Then the solution is transferred to 200 ml stainless steel autoclave and kept 24 hours at room temperature and under hydrogen (4 at). After the excess hydrogen has been blown, the apparatus is disassembled. The content is concentrated to give 3.6 g of the product without purification. A small amount of the unpurified product (0.05 g) is treated with excess diazomethane (solution in ethyl ether). GC Analysis (25 Chirai sil-DEX, 150 ° isotherm, 1 bar Hydrogen, detector ° = 280 ° C, t ° co lumna = 280 ° C) of these solutions shown 90.5% ee and without signal of the initial material. Distillation (78 ° C, 24 mm Hg) produces acid t i 1 (R) -2 -me t i lbut i r i co (1.15 g, 92? [a] - = - 17.2 (pure). 3. Cyclization Enant io se 1 ectia of ethyl-sesame with R-Ti-1 and S-Ti-1: To a solution of both R-3 or S-3 (0.094 g, 0.19 mmoles) in dry toluene (5 ml) add molecular sieves 4A (0.600 g, 1 mm beads) and AgBF4 (0.075 g, 0.39 mmoles) under argon and the mixture is sonified for 10 minutes in the dark. Then a solution of (i-PrO) 2TiCl2 (0.62 ml, 0.302 M in toluene, 0.19 mmol) is added and the resulting dark red solution is stirred at room temperature in the dark for one hour. The mixture is cooled to -22 ° C and a solution of Methyl-Secona (0.300 g, 1 mmol) in toluene (1 ml) is added dropwise. The reaction mixture is then allowed to remain at -20 ° C (frozen) for 3 days. The reaction mixture is rapidly cooled with 20% NaC0. Worked in a usual manner and followed by column chromatography gives 14 -be t-Hi dr ox i -3-p? Ethoxystra-1, 3, 5 (10), 8-tetraen-17-one (0.06 g, 20 %, 36 ee), p. f. = 162.5- 163 ° C (EtOH); [a] D = + 26.9 ° (c = 0.2 in THF) and 3 -Me t ox iestr a- 1, 3, 5 (10), 8, 14 -pen ta in-17 -one (0.17 g, 72% , 70% ee), mp = 108.3 ° C (EtOH), [a] = -70.6 ° (c = 0.12 in THF).

Claims (5)

1. The compounds b ise s t er ida ida s of the general formula I I in which Ri represents hydrogen, alkyl, aciio, fluoro, and X; R ~, where i represents oxygen and sulfur and R5 can be any of hydrogen, to which aryl R2 represents hydrogen and alkyl; the stereochemistry of C-13, C-14 and C-17 can be any of a or β X represents oxygen, hydroxyl trifluoromethylsulfonyloxy, or (Rf,) P, where R6 can be aryl, alkyl and cycloalkyl, R3 represents hydrogen, alkyl, aryl, trialkylsilyl, fluorine and X2Re, wherein X2 represents oxygen and sulfur and Rs represents hydrogen, trifluoromethyl sulphonyl, alkyl, cycloalkyl or aryl. R4 can be any substituent in the 6 or 7 position of the spheroid with the meaning of hydrogen, alkyl, aryl, fluorine, and X R7 where X3 represents oxygen, sulfur otria 1 qui 1 if 1 i 1 oy Ri represents hydrogen, trif 1 uo rorne ti 1 s ul f oni 1 or, alkyl or aryl, and ring B of the spheroid containing no or two double enyl ces, with the proviso that the compound 4, 4 '- di [estr a- 1, 3, 5 (10) - tri-3,17β-diol] is excluded.

2. The enatio- and di-astero-teres derivatives of the compounds of the general formula I, with the proviso that the compound 4,4'-di- [Estra-1, 3, 5 (10) -trien-3 , 17β-diol] is excluded.

3. The use of the compounds of the general formula I of claim 1 and 2 for the preparation of chiral metal complexes

4. The use of the compounds of the general formula I of rei indication 1 and 2 for the preparation of chiral metal complexes containing rsdium, ruthenium, palladium, osmium, iridium, platinum, titanium, aluminum, gold, lanthanides or lanthanide mixture of complexes alkali

5. The use of the compounds of the general formula I of claim 1 and 2 for the preparation of chiral metal complexes containing rhodium, ruthenium, palladium, osmium, iridium, platinum, titanium, aluminum, gold, lanthanides or lanthanide mixture of alkali complexes for all kinds of asymmetric reactions, especially for hydrogenation of electrons, alkenes, anemides, aldehydes or ketones, addition reactions Michael enant ios el ec ti vas, reactions Ene-enan tios el ec ti vas, enanti Ie 1 ecti va of aldehydes and ketones, Diels-Alder reactions enan ti os elec ti ti and hydr os i 1 l a la tion enant iose 1 e ct iva.