CHIRAL SPIRO PHOSPHORUS-NIROGEN-SULPHUR TRIDENTATE LIGAND, PREPARATION METHOD AND APPLICATION THEREOF

Abstract

The present invention relates to a chiral spiro phosphine-nitrogen-sulfur (PNS) tridentate ligand, preparation method and application thereof. The PNS tridentate ligand is a compound represented by Formula I or Formula II, their racemates, optical isomers, or catalytically acceptable salts thereof. The ligand has a primary structure skeleton characterized as a chiral spiro indan skeleton structure with a thio group. The chiral spiro phosphine-nitrogen-sulfur tridentate ligand can be synthesized by reacting racemic or optical active compound 7-diary/alkyl phosphine-7-amino-1,1-spiro-dihydro-indene compound having a spiro-dihydro-indene skeleton as the starting material. The chiral spiro PNS tridentate ligand being complex with transition metal salt can be used in an asymmetric catalytic hydrogenation reaction for catalyzing carbonyl compound. In particular, in asymmetric hydrogenation reaction process, being complex with iridium for catalyzing -alkyl--keto ester can obtain a high catalytic activity (a catalyst amount of 0.0002% mol) and high enantioselectivity (up to 99.9% ee) result. So the present invention has a practical value for industrial and commercial production.

##STR00001##

Claims

1. A chiral spiro phosphine-nitrogen-sulfur tridentate ligand having the structure of Formula I or Formula II, their racemates, optical isomers or their catalytically acceptable salt thereof, ##STR00045## wherein, R.sup.1 is selected from C.sub.1-C.sub.10 alkyl, phenyl, substituted phenyl, 1-naphthyl, 2-naphthyl, heteroaryl or benzyl, and the substituent on said phenyl is C.sub.1-C.sub.10 alkyl or alkoxyl, with a substituent amount ranging from 15, and said heteroaryl is furyl, thienyl or pyridyl; R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are independently selected from H, C.sub.1-C.sub.10 alkyl, phenyl, substituted phenyl, 1-naphthyl, 2-naphthyl, heteroaryl or benzyl, and the substituent on said phenyl is C.sub.1-C.sub.10 alkyl or alkoxyl, with a substituent amount of 15, and said heteroaryl is furyl, thienyl or pyridyl; C.sub.1-C.sub.10 alkoxyl; or R.sup.2R.sup.3, R.sup.4R.sup.5 are incorporated into C.sub.3-C.sub.7 aliphatic ring, aromatic ring; R.sup.2, R.sup.3, R.sup.4 and R.sup.5 can be the same or different; R.sup.6, R.sup.7 are independently selected from H, C.sub.1-C.sub.10 alkyl, C.sub.1-C.sub.10 alkoxy, C.sub.1-C.sub.10 alphatic amido group, and n=03; or when n2, two adjacent R.sup.6 groups or two adjacent R.sup.7 groups can be incorporated into a C.sub.3-C.sub.7 aliphatic ring or aromatic ring and R.sup.6, R.sup.7 can be same or different; R.sup.8, R.sup.9 are independently selected from C.sub.1-C.sub.10 alkyl, C.sub.1-C.sub.10 alkoxy, phenyl, substituted phenyl, 1-naphthyl, 2-naphthyl, heteroaryl or benzyl, and the substituent on said phenyl is C.sub.1-C.sub.10 alkyl or alkoxyl, with a substituent amount of 15, and said heteroaryl is furyl, thienyl or pyridyl; or R.sup.8 and R.sup.9 groups can be incorporated into a ring by C.sub.2-C.sub.4 carbon chain, carbon chain containing N, O, S, aromatic nucleus or heterocyclic aromatic ring; R.sup.8, R.sup.9 can be the same or different.

2. A method for synthesizing the chiral spiro phosphine-nitrogen-sulfur tridentate ligand according to claim 1, which is characterized by that, obtained by reacting racemic or optical active compound 7-diary/alkyl phosphine-7-amino-1,1-spiro-dihydro-indene shown as Formula 1 having a chiral spiro-dihydro-indene skeleton as the starting material via the following reactions: ##STR00046## wherein, R.sup.1R.sup.9 of Formula 1, 2, 3 are defined as claim 1, X of Formula 2 is H, Cl, Br, imidazol or hydroxide radical.

3. A method for synthesizing the chiral spiro phosphine-nitrogen-sulfur tridentate ligand according to claim 1, which is characterized by that, obtained by reacting a racemical or optical active compound 7-diary/alkyl phosphine-7-amino-1,1-spiro-dihydro-indene shown as Formula 1 having a chiral spiro-dihydro-indene skeleton as the starting material via the following reactions: ##STR00047## wherein, R.sup.1R.sup.9 of Formula 1, Formula 4 and Formula II are defined as claim 1.

4. A method for synthesizing the chiral spiro phosphine-nitrogen-sulfur tridentate ligand according to claim 2, wherein, comprising the following steps: the compound of Formula 1 is firstly reacted with the compound of Formula 2 (X is neither H nor OH) in a reactor for 224 hours in the presence of an organic solvent and an alkali to obtain the compound shown as Formula 3; the compound of Formula 3 is then reduced to obtain the chiral spiro phosphine-nitrogen-sulfur tridentate ligand having the structure of Formula I; or the compound of Formula 1 is reacted with the compound of Formula 2 (X is H) in a reactor for 224 hours in the presence of organic solvent and reducing agent directly to obtain the chiral spiro phosphine-nitrogen-sulfur tridentate ligand having the structure of Formula I.

5. The synthesis method according to claim 4, which is characterized by that, the molar ratio among said compound of Formula 1, Formula 2 and reducing agent is in a range of 1:15:110; the temperature of the reaction is 20120 C.

6. A method for synthesizing the chiral spiro phosphine-nitrogen-sulfur tridentate ligand according to claim 2, wherein, comprising the following steps: the compound of Formula 1 is firstly reacted with the compound of Formula 2 (X is OH) in a reactor for 224 hours in the presence of an organic solvent, an alkali and hydroxyl activator to obtain the compound shown as Formula 3; the compound of Formula 3 is then reduced to obtain the chiral spiro phosphine-nitrogen-sulfur tridentate ligand having the structure of Formula I.

7. The synthesis method according to claim 6, which is characterized by that, the molar ratio among said compound of Formula 1, Formula 2, hydroxyl activator and reducing agent is in the range of 1:15:110:110; the temperature of the reaction is 20120 C.

8. A method for synthesizing the chiral spiro phosphine-nitrogen-sulfur tridentate ligand according to claim 2, wherein, comprising the following steps: the compound of Formula 1 is firstly reacted through reduction and amination with the glyoxal-dimethyl-carboxy aldehyde in a reactor in the presence of organic solvent and reducing agent to obtain the compound shown as Formula 4: the compound of Formula 4 is then reacted through replacement reaction with mercaptan (R.sup.8SH and R.sup.9SH) in the presence of Lewis acid to obtain the chiral spiro phosphine-nitrogen-sulfur tridentate ligand having the structure of Formula II.

9. The synthesis method according to claim 8, which is characterized by that, the molar ratio among said compound of Formula 1, glyoxal-dimethyl-carboxy aldehyde, Lewis acid and mercaptan is in the range of 1:15:0.15:110; the temperature of the reaction is 10120 C.

10. The synthesis method according to claim 4, which is characterized by that, the said organic solvent can be any one of methanol, ethanol, propanol, isopropanol, butanol, tetrahydrofuran, toluene, xylene, methyl tert-butyl ether, diethyl ether, dioxane, N,N-dimethyl-formamide, dimethyl sulfoxide, dichloromethane, chloroform, 1,2-dichloroethane or any mixture thereof; said reducing agent can be lithium aluminium hydride, sodium borohydride, sodium triacetyl borohydride or sodium cyanoborohydride; said alkali is an organic base or an inorganic base, in which said organic base can be pyridine, triethylamine, tributyl amine, N-methylmorpholine or N,N-diethyl isopropyl amine; said inorganic base can be sodium hydroxide, potassium hydroxide, sodium carbonate or potassium carbonate; said carboxyl-activating reagent is ethyl chloroformate, isopropyl chloroformate, N,N-dicyclohexyl-carbodiimide or carbonyl diimidazole; said Lewis acid can be titanium tetrachloride, boron trifluoride, indium trichloride, zirconium tetrachloride, tellurium tetrachloride, silicotungstic acid, copper sulfate etc.

11. The application of chiral spiro phosphine-nitrogen-sulfur tridentate ligand, their racemates, optical isomers or catalytically acceptable salts thereof according to claim 1, which is characterized by that, comprising reacting the compounds in the asymmetric catalytic hydrogenation reaction to obtain carbonyl compounds, the said carbonyl compounds are selected from -ketoester compound, -ketoamide compound or simple ketone compound.

12. The application of chiral spiro phosphine-nitrogen-sulfur tridentate ligand, their racemates, optical isomers or catalytically acceptable salts thereof according to claim 11, which is characterized by that, comprising reacting the said chiral spiro phosphine-nitrogen-sulfur tridentate ligand with the transition metal to obtain a complex, further reacting to obtain carbonyl compounds through the asymmetric catalytic hydrogenation reaction, the said carbonyl compounds are selected from -ketoester compound, -ketoamide compound or simple ketone compound.

13. The chiral spiro phosphine-nitrogen-sulfur tridentate ligand, their racemates, optical isomers or catalytically acceptable salts thereof according to claim 1, which is characterized by that, the said compounds is selected from the structures as follows: ##STR00048## ##STR00049## ##STR00050## ##STR00051##

14. The chiral spiro phosphine-nitrogen-sulfur tridentate ligand, their racemates, optical isomers or catalytically acceptable salts thereof according to claim 1, which is characterized by that, the said compounds is selected from the structures as follows: ##STR00052##

15. The method for synthesizing chiral spiro phosphine-nitrogen-sulfur tridentate ligand their racemates, optical isomers or catalytically acceptable salts thereof according to claim 13, which is characterized by that, comprising the following steps: reacting the chiral spiro phosphine-nitrogen-sulfur tridentate ligand with an transitional metal salt at a temperature of 25120 C. for 0.54 hours in the presence of organic solvent; and then stirred for 0.13 hours under the hydrogen atmosphere at the pressure of 0.150 atm to obtain the required chiral catalysts; the molar ratio among the said chiral spiro phosphine-nitrogen-sulfur tridentate ligand and an transitional metallic salt is in the range of 1:12:1; the said iridium metal salt is [Ir(COD)Cl].sub.2 (COD=Cyclooctadiene), [Ir(COD)]BF.sub.4, [Ir(COD).sub.2]PF.sub.6, [Ir(COD).sub.2]SbF.sub.6 or [Ir(COD).sub.2]OTf.

16. The method for synthesizing chiral spiro phosphine-nitrogen-sulfur tridentate ligand, their racemates, optical isomers or catalytically acceptable salts thereof according to claim 13, which is characterized by that, further comprising reacting the said chiral compounds directly to obtain carbonyl compounds through the asymmetric catalytic hydrogenation reaction with or without the treatment of dissolving process to form a storable solid, the said carbonyl compounds are selected from -ketoester compound, -ketoamide compound or simple ketone compound.

17. A method for synthesizing a chiral alcohol compound, which is characterized by that, comprising reacting the ligand complex synthesized in claim 13 as a chiral catalyst with carbonyl compounds and alkalis under the hydrogen atmosphere at the pressure of 0.1100 atm and at the temperature of at 080 C. to obtain the chiral alcohol compound.

18. The method for synthesizing the chiral alcohol compound according to claim 17, which is characterized by that, the molar ratio among the said carbonyl compound and the said ligand is in the range of 100:1500000:1 (the used amount of catalyst is 10.0002 mol %): The concentration of the substrate is 0.00110.0 M.; The said alkali is selected from sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium ethoxide, potassium ethoxide, sodium tert-butoxide, potassium tert-butoxide, lithium tert-butoxide, triethyl amine, tributyl amine or N-methyl morpholine; the concentration of the said alkali is 0.005 M1.0M; the temperature of the reaction is 080 C.

19. The synthesis method according to claim 15 or 17, which is characterized by that, the said organic solvent is any one of methanol, ethanol, propanol, isopropanol, butanol, tetrahydrofuran, toluene, methyl tert-butyl ether, dioxane, DMF, DMSO or any mixture thereof.

Description

DETAILED EMBODIMENTS

[0026] In order to further understand the present invention, preferable embodiments of the present invention will be described by reference to the examples, but it should be appreciated that these descriptions are merely intend to further illustrate the features and advantages of the present invention, rather than limiting the claims of the invention.

Example 1

Synthesis of (R)-7-(bis(3,5-di-tert-butylphenyl)phosphino)-N-(2-(phenylthio)ethyl)-2,2,3,3-tetrahydro-1,1-spirobi[inden]-7-amine

Ia

[0027] ##STR00007##

[0028] (R)-7-bis-(3,5-di-tert-butylphenyl) phosphino-7-amino-1,1-spiroindan (193 mg, 0.3 mmol, pyridine (119 ng, 1.5 mmol) and 2 mL of dichloromethane in 15 mL of dry Schlenk tube. After dissolving the solid at room temperature, the solution of phenylthioacetyl chloride (84 ng, 0.45 mmol) in dichloromethane (2 mL) was added dropwise to the system under ice-cooling. After completion of the adding, stirring the reaction mixture for 2 hours at room temperature, the reaction was complete and analyzed by TLC detecting (petroleum ether:ethyl acetate=10:1). The organic phase was washed with saturated brine, dried over anhydrous magnesium sulfate and allowed to stand. The desiccant was removed by suction filtration, and the filtrate was removed from the solvent by rotary evaporator and the crude product was used directly in the next step.

[0029] Aluminum chloride (120 ng, 0.9 mmol), lithium aluminum hydride (34 mg, 0.9 mmol) and 3 mL of anhydrous ether were weighed in a 15 mL dry Schlenk tube under nitrogen atmosphere and was heated to 40 C. by oil bath. The reaction was reacted to reflux for 0.5 hours and then cooled to room temperature. The ether solution (3 mL) of the crude amide crude product prepared in the previous step was added dropwise to the system using a syringe. After completion of the adding, stirring the reaction mixture for 2 hours at room temperature, the reaction was complete and analyzed by TLC (TLC detection, petroleum ether:ethyl acetate=10:1). The reaction was quenched by the dropwise addition of 2 mL of water to the system under ice-water cooling bath, and the aqueous phase was extracted with ethyl acetate (3 mL3). The organic phase was washed with saturated brine, dried over anhydrous magnesium sulfate and allowed to stand. The desiccant was removed by suction filtration, and the filtrate was removed with a rotary evaporator. The residue was purified by silica gel column chromatography (petroleum ether:ethyl acetate=30:1) to give 147 mg of white solid with 63% yield in two steps.

[0030] Mp 58-60 C., [].sub.D.sup.25 228.8 (c 0.5, CHCl.sub.3). .sup.1H NMR (400 MHz, CDCl.sub.3) 7.30-7.24 (m, 3H), 7.23-7.13 (m, 6H), 7.09 (t, J=7.8 Hz, 2H), 6.93 (dd, J=8.0, 1.6 Hz, 2H), 6.72 (dd, J=7.6, 1.6 Hz, 2H), 6.66 (d, J=7.3 Hz, 1H), 6.09 (d, J=7.9 Hz, 1H), 3.40 (t, J=5.4 Hz, 1H), 3.12-2.66 (m, 7H), 2.66-2.55 (m, 1H), 2.38 (dd, J=22.0, 11.0 Hz, 1H), 2.21-2.05 (m, 3H), 1.19 (s, 18H), 1.15 (s, 18H); .sup.31P NMR (162 MHz, CDCl.sub.3) 18.9 (s). .sup.13C NMR (101 MHz, CDCl.sub.3) 152.6 (d, J=24.5 Hz), 150.0 (d, J=6.8 Hz), 149.9 (d, J=6.0 Hz), 144.7 (d, J=2.6 Hz), 144.1 (d, J=7.3 Hz), 143.8 (d, J=3.4 Hz), 138.5 (d, J=11.9 Hz), 136.4 (d, J=13.3 Hz), 135.8, 135.2, 135.0, 134.0 (d, J=1.9 Hz), 130.1, 129.0, 128.4 (d, J=7.0 Hz), 128.1 (d, J=9.5 Hz), 127.8, 127.1, 126.4, 125.9, 122.4, 121.5, 113.8, 108.0, 61.7 (d, J=3.4 Hz), 41.9, 39.0 (d, J=3.7 Hz), 36.1, 34.9, 34.8, 33.9, 31.6, 31.5, 31.3, 31.0. HRMS (MALDI) Calcd for C.sub.53H.sub.67NPS [M+H].sup.+: 780.4726; Found: 780.4724.

[0031] (In the following Examples, Compounds Ib-Io were prepared via the same processes as Example 1 except of the reactants changed corresponding).

Example 2

Synthesis of (R)-7-(bis(2,6-dimethylphenyl)phosphino)-N-(2-(phenylthio)ethyl)-2,2,3,3-tetrahydro-1,1-spirobi[inden]-7-amine

[0032] ##STR00008##

[0033] Specific process can be found in Example 1, white solid, yield: 65%.

[0034] Mp 5860 C., [].sub.D.sup.25 277.0 (c 0.5, CHCl.sub.3). .sup.1H NMR (400 MHz, CDCl.sub.3) 7.287.08 (m, 8H), 7.03 (t, J=7.6 Hz, 1H), 6.84 (s, 1H), 6.81 (s, 1H), 6.72-6.63 (m, 3H), 6.58 (d, J=7.1 Hz, 2H), 5.92 (d, J=7.9 Hz, 1H), 3.17-3.11 (m, 1H), 3.08-2.96 (m, 4H), 2.78 (td, J=12.9, 6.5 Hz, 1H), 2.68-2.53 (m, 2H), 2.53-2.43 (m, 1H), 2.43-2.33 (m, 2H), 2.33-2.23 (m, 1H), 2.17 (s, 6H), 2.16 (s, 6H); .sup.31P NMR (162 MHz, CDCl.sub.3) 22.6 (s); .sup.13C NMR (101 MHz, CDCl.sub.3) 153.1 (d, J=25.3 Hz), 144.6 (d, J=2.8 Hz), 144.1 (d, J=7.7 Hz), 143.5 (d, J=1.8 Hz), 139.5 (d, J=13.0 Hz), 137.3 (d, J=6.0 Hz), 137.1 (d, J=8.1 Hz), 136.2 (d, J=13.3 Hz), 135.8, 135.0, 134.8, 134.4 (d, J=2.9 Hz), 133.4 (d, J=3.4 Hz), 132.5, 132.2, 130.9, 130.7, 130.4, 130.1, 129.5, 129.0, 128.1, 127.5, 126.4, 126.0, 113.7, 107.9, 61.7 (d, J=3.2 Hz), 41.5, 39.9 (d, J=6.0 Hz), 36.3, 33.8, 31.5, 31.1, 21.4. HRMS (MALDI) Calcd for C.sub.41H.sub.43NPS [M+H].sup.+: 612.2848; Found: 612.2845.

Example 3

Synthesis of (R)-7-(bis(3,5-di-tert-butylphenyl)phosphino)-N-(2-(phenylthio)ethyl)-2,2,3,3-tetrahydro-1,1-spirobi[inden]-7-amine

Ic

[0035] ##STR00009##

[0036] Specific process can be found in Example 1, white solid, yield: 51%.

[0037] Mp 55-58 C., [].sub.D.sup.25 245.5 (c 0.5, CHCl.sub.3). .sup.1H NMR (400 MHz, CDCl.sub.3) 7.31-6.91 (m, 19H), 6.65 (d, J=7.3 Hz, 1H), 5.93 (d, J=7.9 Hz, 1H), 3.27-3.18 (m, 1H), 3.11-2.93 (m, 4H), 2.93-2.81 (m, 1H), 2.68 (t, J=6.5 Hz, 2H), 2.53-2.33 (m, 3H), 2.32-2.23 (m, 1H), 2.18-2.08 (m, 1H); .sup.31P NMR (162 MHz, CDCl.sub.3) 22.3 (s); .sup.13C NMR (101 MHz, CDCl.sub.3) 153.3 (d, J=25.3 Hz), 144.6 (d, J=3.1 Hz), 144.3 (d, J=7.8 Hz), 143.4, 139.7 (d, J=13.9 Hz), 136.8 (d, J=14.0 Hz), 135.6, 134.5 (d, J=2.5 Hz), 134.34, 134.25, 134.1, 134.0, 133.3, 133.2 (d, J=3.5 Hz), 133.1, 130.0, 129.0, 128.4 (d, J=3.6 Hz), 128.1 (d, J=5.5 Hz), 128.0 (d, J=7.3 Hz), 127.7 (d, J=9.9 Hz), 126.4, 126.3, 113.8, 108.0, 61.7 (d, J=3.2 Hz), 41.3, 40.0 (d, J=5.3 Hz), 36.2, 33.9, 31.5, 31.1. HRMS (MALDI) Calcd for C.sub.37H.sub.35NPS [M+H]: 556.2222; Found: 556.2216.

Example 4

Synthesis of (R)-7-(bis(3,5-di-tert-butylphenyl)phosphino)-N-(2-((2,6-dimethylphenyl)thio)ethyl)-2,2,3,3-tetrahydro-1,1-spirobi[inden]-7-amine

Id

[0038] ##STR00010##

[0039] Specific process can be found in Example 1, white solid, yield: 69%.

[0040] Mp 71-74 C., [].sub.D.sup.25 159.2 (c 0.5, CHCl.sub.3). .sup.1H NMR (400 MHz, CDCl.sub.3) 7.31-7.27 (m, 2H), 7.23-7.16 (m, 2H), 7.12-7.02 (m, 5H), 6.94 (dd, J=8.0, 1.6 Hz, 2H), 6.73 (dd, J=7.6, 1.6 Hz, 2H), 6.66 (d, J=7.4 Hz, 1H), 6.03 (d, J=8.0 Hz, 1H), 3.42-3.35 (m, 1H), 3.13-2.87 (m, 3H), 2.86-2.72 (m, 2H), 2.55-2.44 (m, 3H), 2.39 (s, 6H), 2.20-2.06 (m, 3H), 1.20 (s, 18H), 1.16 (s, 18H); .sup.31P NMR (162 MHz, CDCl.sub.3) 18.8 (s); .sup.13C NMR (101 MHz, CDCl.sub.3) 152.6 (d, J=24.7 Hz), 150.0 (d, J=6.9 Hz), 149.9 (d, J=6.1 Hz), 144.6 (d, J=3.1 Hz), 144.1 (d, J=7.4 Hz), 143.9 (d, J=3.4 Hz), 143.3, 138.4 (d, J=11.8 Hz), 136.4 (d, J=13.5 Hz), 135.1 (d, J=23.2 Hz), 133.9 (d, J=1.7 Hz), 133.2, 132.4 (d, J=3.3 Hz), 128.4, 128.3 (d, J=6.0 Hz), 128.2, 128.1 (d, J=2.5 Hz), 127.9, 127.1, 126.0, 122.3, 121.5, 113.7, 107.8, 61.7 (d, J=3.2 Hz), 42.4, 38.9 (d, J=3.6 Hz), 36.0, 35.1, 34.9, 34.8, 31.6, 31.5, 31.3, 31.0, 22.2. HRMS (MALDI) Calcd for C.sub.55H.sub.71NPS [M+H].sup.+: 808.5039; Found: 808.5042.

Example 5

Synthesis of (R)-7-(bis(3,5-di-tert-butylphenyl)phosphino)-N-(2-((3,5-dimethylphenyl)thio)ethyl)-2,2,3,3-tetrahydro-1,1-spirobi[inden]-7-amine (Ie)

[0041] ##STR00011##

[0042] Specific process can be found in Example 1, white solid, yield: 65%.

[0043] Mp 60-62 C., [].sub.D.sup.25 229.0 (c 0.5, CHCl.sub.3). .sup.1H NMR (400 MHz, CDCl.sub.3) 7.28-7.13 (m, 4H), 7.12-7.05 (m, 2H), 6.92 (d, J=8.0 Hz, 2H), 6.82 (s, 2H), 6.77 (s, 1H), 6.72 (d, J=7.5 Hz, 2H), 6.65 (d, J=7.4 Hz, 1H), 6.09 (d, J=8.0 Hz, 1H), 3.41 (t, J=5.5 Hz, 1H), 3.09-2.57 (m, 8H), 2.43-2.31 (m, 1H), 2.23 (s, 6H), 2.18-2.06 (m, 3H), 1.18 (s, 18H), 1.14 (s, 18H); .sup.31P NMR (162 MHz, CDCl.sub.3) 18.8 (s); .sup.13C NMR (101 MHz, CDCl.sub.3) 152.6 (d, J=24.5 Hz), 150.0 (d, J=6.6 Hz), 149.9 (d, J=5.9 Hz), 144.6 (d, J=2.8 Hz), 144.1 (d, J=7.4 Hz), 143.8 (d, J=3.2 Hz), 138.5, 136.3, 135.3, 134.9, 133.9, 132.6 (d, J=3.7 Hz), 128.4, 128.3 (d, J=6.6 Hz), 128.1, 127.9, 127.7, 127.1, 125.9, 123.3, 122.3, 121.5, 113.7, 107.9, 61.7 (d, J=3.0 Hz), 42.0, 39.0 (d, J=3.7 Hz), 36.0, 34.9, 34.8, 33.7, 31.6, 31.5, 31.3, 30.9, 21.3. HRMS (MALDI) Calcd for C.sub.55H.sub.71NPS [M+H].sup.+: 808.5039; Found: 808.5039.

Example 6

Synthesis of (R)-7-(bis(3,5-di-tert-butylphenyl)phosphino)-N-(2-(p-tolylthio)ethyl)-2,2,3,3-tetrahydro-1,1-spirobi[inden]-7-amine (If)

[0044] ##STR00012##

[0045] Specific process can be found in Example 1, white solid, yield: 70%.

[0046] Mp 60-62 C. [].sub.D.sup.25 236.1 (c 0.5, CHCl.sub.3). .sup.1H NMR (400 MHz, CDCl.sub.3) 7.29-7.14 (m, 4H), 7.13-6.99 (m, 6H), 6.92 (d, J=8.0 Hz, 2H), 6.72 (d, J=7.5 Hz, 2H), 6.65 (d, J=7.3 Hz, 1H), 6.06 (d, J=7.9 Hz, 1H), 3.40 (t, J=5.3 Hz, 1H), 3.09-2.53 (m, 8H), 2.44-2.33 (m, 1H), 2.28 (s, 3H), 2.17-2.06 (m, 3H), 1.18 (s, 18H), 1.14 (s, 18H); .sup.31P NMR (162 MHz, CDCl.sub.3) 18.9 (s); .sup.13C NMR (101 MHz, CDCl.sub.3) 152.5 (d, J=25.0 Hz), 149.9 (d, J=6.5 Hz), 149.8 (d, J=5.9 Hz), 144.5 (d, J=2.3 Hz), 143.9 (d, J=7.7 Hz), 143.7 (d, J=3.2 Hz), 138.3 (d, J=11.4 Hz), 137.2, 136.5, 136.3 (d, J=13.1 Hz), 135.1, 134.9, 133.8 (d, J=1.8 Hz), 132.5 (d, J=3.8 Hz), 131.7, 131.0, 129.6, 129.2, 128.3 (d, J=6.8 Hz), 128.0 (d, J=5.8 Hz), 127.8, 127.0, 125.8, 122.2, 121.4, 113.6, 107.8, 61.6 (d, J=3.3 Hz), 41.7, 38.9 (d, J=4.3 Hz), 36.0, 34.8, 34.7, 34.5, 31.5, 31.3, 31.2, 30.8, 21.0. HRMS (MALDI) Calcd for CH.sub.69NPS [M+H].sup.+: 794.4883; Found: 794.4886.

Example 7

Synthesis of (R)-7-(bis(3,5-di-tert-butylphenyl)phosphino)-N-(2-(naphthalen-2-ylthio)ethyl)-2,2,3,3-tetrahydro-1,1-spirobi[inden]-7-amine (Ig)

[0047] ##STR00013##

[0048] Specific process can be found in Example 1, white solid. yield:

[0049] Mp 69-71 C., [].sub.D.sup.25 188.1 (c 0.5, CHCl.sub.3). .sup.1H NMR (400 MHz, CDCl.sub.3) 7.75 (d, J=7.6 Hz, 1H), 7.66 (t, J=8.5 Hz, 2H), 7.60 (s, 1H), 7.48-7.37 (m, 2H), 7.31-7.05 (m, 7H), 6.93 (d, J=8.0 Hz, 2H), 6.72 (d, J=7.5 Hz, 2H), 6.66 (d, J=7.3 Hz 1H), 6.11 (d, J=7.9 Hz, 1H), 3.51-3.41 (m, 1H), 3.09-2.75 (m, 7H), 2.72-2.60 (m, 1H), 2.46-2.32 (m, 1H), 2.20-2.04 (m, 3H), 1.15 (s, 18H), 1.14 (s, 18H); .sup.31P NMR (162 MHz, CDCl.sub.3) 18.82 (s); .sup.13C NMR (101 MHz, CDCl.sub.3) 152.6 (d, J=24.5 Hz), 150.0 (d, J=6.9 Hz), 149.9 (d, J=6.1 Hz), 144.7 (d, J=2.3 Hz), 144.1 (d, J=7.5 Hz), 143.8 (d, J=3.1 Hz), 138.5 (d, J=11.8 Hz), 136.3 (d, J=13.1 Hz), 135.1 (d, J=22.9 Hz), 134.0, 133.8, 133.4, 132.7 (d, J=3.3 Hz), 132.0, 128.44, 128.36, 128.1 (d, J=9.6 Hz), 128.0, 127.9, 127.8, 127.2, 127.1, 126.6, 126.0, 125.8, 122.4, 121.5, 113.9, 108.0, 61.7 (d, J=3.2 Hz), 42.0, 39.0 (d, J=4.0 Hz), 36.1, 34.9, 34.8, 33.8, 31.6, 31.5, 31.3, 30.9. HRMS (ESI) Calcd for C.sub.TH.sub.69NPS [M+H].sup.+: 830.4883; Found: 830.4885.

Example 8

Synthesis of (R)-7-(bis(3,5-di-tert-butylphenyl)phosphino)-N-(2-((4-methoxyphenyl)thio)ethyl)-2,2,3,3-tetrahydro-1,1-spirobi[inden]-7-amine (Ih)

[0050] ##STR00014##

[0051] Specific process can be found in Example 1, white solid. yield: 70%.

[0052] Mp 124-126 C., [].sub.D.sup.25 194.8 (c 0.5, CHCl.sub.3).sup.1H NMR (400 MHz, CDCl.sub.3) 7.32-7.27 (m, 2H), 7.24-7.15 (m, 4H), 7.14-7.05 (m, 2H), 6.92 (d, J=8.0 Hz, 2H), 6.80-6.70 (m, 4H), 6.66 (d, J=7.3 Hz, 1H), 6.06 (d, J=7.9 Hz, 1H), 3.78 (s, 3H), 3.44-3.37 (m, 1H), 3.12-2.74 (m, 5H), 2.72-2.53 (min, 3H), 2.41 (dd, J=22.1, 10.8 Hz, 1H), 2.22-2.08 (m, 3H), 1.19 (s, 18H), 1.16 (s, 18H). .sup.31P NMR (162 MHz, CDCl.sub.3) 18.78 (s). .sup.13C NMR (101 MHz, CDCl.sub.3) 159.2, 152.6 (d, J=24.5 Hz), 150.0 (d, J=4.4 Hz), 149.9 (d, J=3.6 Hz), 144.6 (d, J=2.7 Hz), 144.1 (d, J=7.4 Hz), 143.8 (d, J=3.1 Hz), 138.4 (d, J=11.9 Hz), 136.5 (d, J=13.3 Hz), 135.2 (d, J=23.5 Hz), 134.1 (s), 133.9 (d, J=2.3 Hz), 132.5 (d, J=3.5 Hz), 128.4 (d, J=9.5 Hz), 128.1, 127.9, 127.1, 125.9, 125.6, 122.3, 121.5, 114.6, 113.7, 107.8, 61.7 (d, J=3.4 Hz), 55.4, 41.7, 38.98 (d, J=3.9 Hz), 36.2, 35.8, 34.9, 34.8, 31.6, 31.5, 31.3, 31.0. HRMS (MALDI) Calcd for C.sub.54H.sub.69NOPS [M+H].sup.+: 810.4832; Found: 810.4836.

Example 9

Synthesis of (R)-7-(bis(3,5-di-tert-butylphenyl)phosphino)-N-(2-((2,6-dichlorophenyl)thio)ethyl)-2,2,3,3-tetrahydro-1,1-spirobi[inden]-7-amine (Ii)

[0053] ##STR00015##

[0054] Specific process can be found in Example 1, white solid yield:

[0055] Mp 78-80 C., [].sub.D.sup.25 134.7 (c 0.5, CHCl.sub.3). .sup.1H NMR (400 MHz, CDCl.sub.3) 7.36-7.27 (m, 4H), 7.24-7.18 (m, 2H), 7.17-7.07 (m, 3H), 6.97 (dd, J=8.0, 1.1 Hz, 2H), 6.75 (dd, J=7.5, 1.1 Hz, 2H), 6.68 (d, J=7.3 Hz, 1H), 6.07 (d, J=8.0 Hz, 1H), 3.60 (t, J=5.6 Hz, 1H), 3.14-3.04 (m, 2H), 3.03-2.90 (m, 1H), 2.90-2.66 (m, 4H), 2.53-2.41 (m, 2H), 2.27-2.11 (m, 3H), 1.20 (s, 18H), 1.17 (s, 18H); .sup.31P NMR (162 MHz, CDCl.sub.3) 19.0 (s); .sup.13C NMR (101 MHz, CDCl.sub.3) 152.7 (d, J=25.0 Hz), 150.0 (d, J=3.8 Hz), 149.9 (d, J=3.0 Hz), 144.7 (d, J=2.6 Hz), 144.1 (d, J=7.6 Hz), 143.4 (d, J=3.4 Hz), 141.9, 138.6 (d, J=12.0 Hz), 136.5 (d, J=13.2 Hz), 135.0 (d, J=23.0 Hz), 134.1 (d, J=2.5 Hz), 132.8, 130.0, 128.6, 128.3 (d, J=3.3 Hz), 128.0 (d, J=10.6 Hz), 127.8, 127.1, 126.1, 122.2, 121.4, 113.7, 107.6, 61.7 (d, J=3.3 Hz), 41.8, 39.1 (d, J=3.9 Hz), 35.9, 35.2, 34.9, 34.8, 31.6, 31.5, 31.3, 31.0. HRMS (ESI) Calcd for C.sub.53H.sub.65Cl.sub.2NPS [M+H].sup.+: 848.3947; Found: 848.3928.

Example 10

Synthesis of (R)-7-(bis(3,5-di-tert-butylphenyl)phosphino)-N-(2-((4-chlorophenyl)thio)ethyl)-2,2,3,3-tetrahydro-1,1-spirobi[inden]-7-amine (Ij)

[0056] ##STR00016##

[0057] Specific process can be found in Example 1, white solid, yield:

[0058] Mp 129-131 C., [].sub.D.sup.25 240.3 (c 0.5, CHCl.sub.3). .sup.1H NMR (400 MHz, CDCl.sub.3) 7.30-7.13 (m, 6H), 7.12-7.06 (m, 4H), 6.92 (dd, J=8.0, 1.3 Hz, 2H), 6.71 (dd, J=7.5, 1.3 Hz, 2H), 6.67 (d, J=7.4 Hz, 1H), 6.08 (d, J=7.9 Hz, 1H), 3.39 (t, J=5.5 Hz, 1H), 3.10-2.64 (m, 7H), 2.63-2.52 (m, 1H), 2.42-2.30 (m, 1H), 2.19-2.06 (m, 3H), 1.18 (s, 18H), 1.14 (s, 18H); .sup.31P NMR (162 MHz, CDCl.sub.3) 18.9 (s); .sup.13C NMR (101 MHz, CDCl.sub.3) 152.6 (d, J=24.5 Hz), 150.1 (d, J=7.0 Hz), 150.0 (d, J=6.0 Hz), 144.7 (d, J=3.0 Hz), 144.1 (d, J=7.4 Hz), 143.7 (d, J=3.2 Hz), 138.4 (d, J=11.7 Hz), 136.3 (d, J=13.5 Hz), 135.1 (d, J=23.6 Hz), 134.3, 134.0, 132.7 (d, J=3.7 Hz), 132.4, 131.6, 129.1, 128.6, 128.4 (d, J=3.9 Hz), 128.1 (d, J=16.4 Hz), 127.8, 127.1, 125.9, 122.4, 121.5, 114.0, 107.9, 61.7 (d, J=3.2 Hz), 41.8, 39.0 (d, J=4.0 Hz), 36.1, 34.94, 34.85, 34.2, 31.6, 31.5, 31.3, 31.0. HRMS (ESI) Calcd for C.sub.53H.sub.66ClNPS [M+H].sup.+: 814.4337; Found: 814.4331.

Example 11

Synthesis of (R)-7-(bis(3,5-di-tert-butylphenyl)phosphino)-N-(2-((4-(trifluoromethyl)phenyl)thio)ethyl)-2,2,3,3-tetrahydro-1,1-spirobi[inden]-7-amine (Ik)

[0059] ##STR00017##

[0060] Specific process can be found in Example 1, white solid, yield:

[0061] Mp 96-98 C., [].sub.D.sup.25 376.1 (c 0.5, CHCl.sub.3). .sup.1H NMR (400 MHz, CDCl.sub.3) 7.43 (d, J=8.1 Hz, 2H), 7.29-7.08 (m, 9H), 6.93 (d, J=8.0 Hz, 2H), 6.73-6.65 (m, 3H), 6.11 (d, J=7.9 Hz, 1H), 3.44-3.36 (m, 1H), 3.11-2.74 (m, 7H), 2.67-2.56 (m, 1H), 2.39-2.27 (m, 1H), 2.20-2.05 (m, 3H), 1.18 (s, 18H), 1.14 (s, 18H); .sup.31P NMR (162 MHz, CDCl.sub.3) 19.0 (s); .sup.13C NMR (101 MHz, CDCl.sub.3) 152.6 (d, J=24.8 Hz), 150.1 (d, J=7.1 Hz), 150.0 (d, J=5.8 Hz), 144.8 (d, J=2.5 Hz), 144.1 (d, J=7.5 Hz), 143.7 (d, J=3.4 Hz), 141.7, 138.4 (d, J=11.9 Hz), 136.2 (d, J=12.9 Hz), 135.1 (d, J=23.3 Hz), 134.0 (d, J=1.9 Hz), 132.7 (d, J=3.2 Hz), 128.4 (d, J=2.9 Hz), 128.2, 127.9 (d, J=19.7 Hz), 127.2, 125.9, 125.7 (d, J=3.7 Hz), 122.5, 121.5, 114.2, 108.0, 61.7 (d, J=3.3 Hz), 41.9, 38.9 (d, J=3.9 Hz), 36.0, 34.94, 34.84, 32.8, 31.6, 31.4, 31.3, 30.9; HRMS (ESI) Calcd for C.sub.54H.sub.66F.sub.3NPS [M+H].sup.+: 848.4600; Found: 848.4605.

Example 12

Synthesis of (R)-7-(bis(3,5-di-text-butylphenyl)phosphino)-N-(2-(ethylthio)ethyl)-2,2,3,3-tetrahydro-1,1-spirobi[inden]-7-amine (If)

[0062] ##STR00018##

[0063] Specific process can be found in Example 1, white solid, yield:

[0064] Mp 94-96 C., [].sub.D.sup.25 172.3 (c 0.5, CHCl.sub.3). .sup.1H NMR (400 MHz, CDCl.sub.3) 7.33-7.24 (m, 2H), 7.23-7.06 (m, 4H), 6.94 (d, J=7.9 Hz, 2H), 6.72 (d, J=7.5 Hz, 2H), 6.67 (d, J=7.3 Hz, 1H), 6.16 (d, J=7.9 Hz, 1H), 3.43-3.33 (m, 1H), 3.13-2.72 (m, 5H), 2.68-2.55 (m, 1H), 2.46-2.25 (m, 5H), 2.21-2.05 (m, 3H), 1.22 (s, 18H), 1.17-1.08 (m, 21H); .sup.31P NMR (162 MHz, CDCl.sub.3) 18.8 (s); .sup.13C NMR (101 MHz, CDCl.sub.3) 152.6 (d, J=24.7 Hz), 150.0 (d, J=7.2 Hz), 149.9 (d, J=6.1 Hz), 144.6 (d, J=2.5 Hz), 144.2 (d, J=3.1 Hz), 144.1 (d, J=7.2 Hz), 138.4 (d, J=11.5 Hz), 136.4 (d, J=13.5 Hz), 135.2, 134.9, 133.9, 132.5 (d, J=3.6 Hz), 128.4 (d, J=2.7 Hz), 128.1 (d, J=10.5 Hz), 127.9, 127.1, 125.9, 122.3, 121.5, 113.8, 108.0, 61.7 (d, J=3.2 Hz), 42.8, 38.9 (d, J=3.9 Hz), 36.0, 35.0, 34.8, 31.6, 31.5, 31.4, 31.3, 30.9, 25.9, 15.0. HRMS (ESI) Calcd for C.sub.49H.sub.67NPS [M+H].sup.+: 732.4726; Found: 732.4728.

Example 13

Synthesis of (R)-7-(bis(3,5-di-tert-butylphenyl)phosphino)-N-(2-(tert-butylthio)ethyl)-2,2,3,3-tetrahydro-1,1-spirobi[inden]-7-amine (Im)

[0065] ##STR00019##

[0066] Specific process can be found in Example 1, white solid, yield: 76%.

[0067] Mp 152-155 C., [].sub.D.sup.25 196.5 (c 0.5, CHCl.sub.3). .sup.1H NMR (400 MHz, CDCl.sub.3) 7.31-7.24 (m, 2H), 7.24-7.07 (m, 4H), 6.96-6.90 (m, 2H), 6.78-6.71 (m, 2H), 6.66 (d, J=7.3 Hz, 1H), 6.16 (d, J=7.9 Hz, 1H), 3.50-3.40 (m, 1H), 3.14-2.98 (m, 2H), 2.95-2.83 (m, 2H), 2.81-2.70 (m, 1H), 2.65-2.54 (m, 1H), 2.47-2.37 (m, 3H), 2.20-2.02 (m, 3H), 1.22 (s, 18H), 1.19 (s, 9H), 1.16 (s, 18H); .sup.31P NMR (162 MHz, CDCl.sub.3) 18.4 (s); .sup.13C NMR (101 MHz, CDCl.sub.3) 152.6 (d, J=24.8 Hz), 149.94 (d, J=3.4 Hz), 149.88 (d, J=3.0 Hz), 144.6 (d, J=2.2 Hz), 144.3 (d, J=3.4 Hz), 144.0 (d, J=7.5 Hz), 138.3 (d, J=11.8 Hz), 136.4 (d, J=13.0 Hz), 135.0 (d, J=23.5 Hz), 133.8 (s), 132.3 (d, J=3.3 Hz), 128.4 (s), 128.3 (d, J=11.0 Hz), 128.1 (d, J=9.9 Hz), 127.1 (s), 125.9 (s), 122.2 (s), 121.5 (s), 113.7 (s), 108.0 (s), 61.7 (d, J=3.1 Hz), 42.7 (s), 41.8 (s), 38.85 (d, J=3.6 Hz), 35.92 (s), 34.94 (s), 34.8 (s), 31.6 (s), 31.5 (s), 31.3 (s), 31.1 (s), 30.9 (s), 28.5 (s). HRMS (MALDI) Calcd for C.sub.51H.sub.71NPS [M+H].sup.+: 760.5039; Found: 760.5036.

Example 14

Synthesis of (R)-7-(bis(3,5-di-tert-butylphenyl)phosphino)-N-(2-(cyclohexylthio)ethyl)-2,2,3,3-tetrahydro-1,1-spirobi[inden]-7-amine (In)

[0068] ##STR00020##

[0069] Specific process can be found in Example 1, colorless oily liquid, yield: 45%.

[0070] Mp [].sub.D.sup.25 186.8 (c 0.5, CHCl.sub.3). .sup.1H NMR (400 MHz, CDCl.sub.3) 7.31-7.25 (m, 2H), 7.23-7.05 (m, 4H), 6.93 (dd, J=8.0, 1.8 Hz, 2H), 6.73 (dd, J=7.5, 1.8 Hz, 2H), 6.66 (d, J=7.4 Hz, 1H), 6.14 (d, J=7.9 Hz, 1H), 3.39 (t, J=5.4 Hz 1H), 3.11-2.73 (m, 5H), 2.66-2.56 (m, 1H), 2.48-2.27 (m, 4H), 2.19-2.05 (m, 3H), 1.85-1.77 (m, 2H), 1.75-1.66 (m, 2H), 1.62-1.55 (m, 1H), 1.23-1.13 (m, 41H). .sup.31P NMR (162 MHz, CDCl.sub.3) 18.72 (s). .sup.13C NMR (101 MHz, CDCl.sub.3) 152.6 (d, J=24.5 Hz), 149.97 (d, J=4.3 Hz), 149.91 (d, J=3.7 Hz), 144.6 (d, J=2.6 Hz), 144.2 (d, J=3.2 Hz), 143.9 (d, J=7.3 Hz), 138.4 (d, J=11.9 Hz), 136.5 (d, J=13.4 Hz), 135.1 (d, J=23.5 Hz), 133.8 (d, J=2.3 Hz), 132.5 (d, J=3.5 Hz), 128.4 (d, J=11.1 Hz), 128.1 (d, J=3.9 Hz), 127.9 (s), 127.0, 125.9, 122.2, 121.5, 113.7, 108.0, 61.7 (d, J=3.3 Hz), 43.3, 42.9, 38.9 (d, J=3.8 Hz), 36.1, 34.9, 34.8, 33.9, 31.6, 31.5, 31.3, 31.0, 30.0, 26.1, 25.9. HRMS (MALDI) Calcd for C.sub.53H.sub.73NPS [M+H].sup.+: 786.5196; Found: 786.5198.

Example 15

Synthesis of (R)N-(2-(benzylthio)ethyl)-7-(bis(3,5-di-tert-butylphenyl)phosphino)-2,2,3,3-tetrahydro-1,1-spirobi[inden]-7-amine (Io)

[0071] ##STR00021##

[0072] Specific process can be found in Example 1, white solid, yield: 70%.

[0073] Mp 47-49 C., [].sub.D.sup.25 168.8 (c 0.5, CHCl.sub.3). .sup.1H NMR (400 MHz, CDCl.sub.3) 7.32-7.07 (m, 11H), 6.94 (d, J=8.0 Hz, 2H), 6.73 (d, J=7.5 Hz, 2H), 6.67 (d, J=7.4 Hz, 1H), 6.11 (d, J=7.9 Hz, 1H), 3.52 (d, J=13.4 Hz, 1H), 3.47 (d, J=13.5 Hz, 1H), 3.36 (t, J=5.2 Hz, 1H), 3.14-2.72 (m, 5H), 2.58 (td, J=11.8, 6.0 Hz, 1H), 2.47-2.28 (m, 2H), 2.28-2.07 (m, 4H), 1.21 (s, 18H), 1.16 (s, 18H); .sup.31P NMR (162 MHz, CDCl.sub.3) 18.8; .sup.13C NMR (101 MHz, CDCl.sub.3) 152.6 (d, J=24.5 Hz), 150.0 (d, J=7.5 Hz), 149.9 (d, J=6.9 Hz), 144.6 (d, J=2.8 Hz), 144.1 (d, J=3.9 Hz), 144.0, 138.5, 138.4 (d, J=3.3 Hz), 136.5, 136.4, 135.2, 135.0, 133.9 (d, J=1.9 Hz), 132.6 (d, J=3.5 Hz), 128.9, 128.6, 128.4 (d, J=3.7 Hz), 128.1 (d, J=8.5 Hz), 127.9, 127.1 (d, J=5.7 Hz), 125.9, 122.3, 121.5, 61.7 (d, J=3.2 Hz), 42.4, 38.9 (d, J=4.0 Hz), 36.2 (d, J=17.2 Hz), 34.9 (d, J=10.5 Hz), 31.6, 31.5, 31.3, 31.0, 29.9. HRMS (MALDI) Calcd for C.sub.54H.sub.69NPS [M+H].sup.+: 794.4883; Found: 794.4885.

Example 16

Synthesis of (R)N-((1,3-dithian-2-yl)methyl)-7-(bis(3,5-di-tert-butylphenyl)phosphino)-2,2,3,3-tetrahydro-1,1-spirobi[inden]-7-anine (IIa)

[0074] ##STR00022##

[0075] To a dry and clean 15 mL Schlenk tube equipped with magnetic stirring, was added (R)-7-di-(3,5-di-tert-butylphenyl) phosphino-7-amino-1,1-spiroindane (193 mg, 0.3 mmol) and 10% palladium(30 mL %, 58 mg). the system was replaced with argon atmosphere, and anhydrous ethanol (3 mL) and aqueous glyoxal dimethyl acetal (60% aq., 0.66 mL, 3.0 mmol) were adding sequencely and stirred well. The system quickly replaced with hydrogen atmosphere, the reaction mixture was reacted for 4 hours at room temperature, the reaction was reacted complete and analyzed by TLC detecting. The reaction system was filtered through celite to remove palladium carbon. The filtrate was removed with a rotary evaporator. The residue was diluted with 5 mL of ethyl acetate, washed with saturated brine, dried over anhydrous magnesium sulfate and allowed to stand. The solvent was removed by filtration and the filtrate was removed from the solvent by rotary evaporator. The crude product was used directly in the next step to replace the reaction.

[0076] The crude product obtained above was added to a dry 15 mL Schlenk tube equipped with a magnetic stirrer in a nitrogen atmosphere, indium trichloride (139 mg, 0.63 mmol), 1,3-propanedithiol (39 mg, 0.36 mmol) and 3 mL of 1,2-dichloroethane. The solution was heated to 85 C. by oil bath for 2 hours and the reaction was reacted complete and analyzed by TLC detecting. The reaction mixture was cooled to room temperature, quenched with 10% aqueous sodium hydroxide solution (2 mL). The aqueous phase was extracted with dichloromethane (3 mL3). The organic phase was washed with saturated brine, dried over anhydrous magnesium sulfate and allowed to stand. The desiccant was removed by suction filtration, and the filtrate was removed with a rotary evaporator. The residue was purified by silica gel column chromatography (petroleum ether:ethyl acetate=30:1) to give 143 mg of white solid with 65% yield.

[0077] Mp 115-118 C., [].sub.D.sup.25 179.9 (c 0.5, CHCl.sub.3). .sup.1H NMR (400 MHz, CDCl.sub.3) 7.29-7.25 (m, 2H), 7.24 (t, J=1.7 Hz, 1H), 7.15 (m, 2H), 7.10-7.05 (m, 1H), 6.92 (dd, J=7.9, 1.8 Hz, 2H), 6.78 (dd, J=7.7, 1.8 Hz, 2H), 6.66 (d, J=7.3 Hz, 1H), 6.23 (d, J=7.9 Hz, 1H), 4.19 (dd, J=6.9, 4.5 Hz, 1H), 3.38-3.29 (m, 1H), 3.18 (s, 3H), 3.03 (s, 3H), 3.10-2.92 (m, 3H), 2.91-2.83 (m, 1H), 2.73-2.61 (m, 2H), 2.43-2.32 (m, 1H), 2.08 (dd, J=12.7, 7.3 Hz, 2H), 2.03-1.91 (m, 1H), 1.20 (s, 18H), 1.17 (s, 18H); .sup.31P NMR (162 MHz, CDCl.sub.3) 17.8 (s); .sup.13C NMR (101 MHz, CDCl.sub.3) 152.3 (d, J=24.4 Hz), 150.0 (d, J=2.8 Hz), 149.9 (d, J=3.1 Hz), 144.6 (d, J=2.2 Hz), 144.5 (d, J=3.6 Hz), 144.0 (d, J=7.3 Hz), 137.9 (d, J=11.3 Hz), 136.6 (d, J=13.5 Hz), 135.4, 135.1, 133.5 (d, J=1.6 Hz), 132.4 (d, J=3.2 Hz), 128.5, 128.3 (d, J=7.6 Hz), 128.2, 127.0, 125.6, 122.1, 121.7, 113.9, 108.1, 103.2, 61.7 (d, J=3.2 Hz), 54.2, 53.7, 45.1, 38.5 (d, J=3.3 Hz), 36.2, 35.0, 34.9, 31.6, 31.5, 31.3, 30.9. HRMS (MALDI) Calcd for C.sub.49H.sub.67NO.sub.2P [M+H].sup.+: 732.4904; Found: 732.4911.

Example 17

Synthesis of (R)N-((1,3-dithian-2-yl)methyl)-7-(diphenylphosphino)-2,2,3,3-tetrahydro-1,1-spirobi[inden]-7-amine (IIb)

[0078] ##STR00023##

[0079] To a dry and clean Schlenk tube equipped with a magnetic stirrer, was added (R)-7-diphenylphosphino-7-amino-1,1-spiroindan (126 mg, 0.3 mmol), sodium triacetoxyborohydride (318 mg, 1.5 mmol). The system was replaced with argon atmosphere, followed by the addition of 1,2-dichloroethane (3 mL) and glyoxal dimethyl acetal (60% aq., 0.33 mL, 1.5 mmol) in sequence and stirred well. The reaction solution was heated to 85 C. for 2 hours by oil bath and the reaction was reacted complete and analyzed by TLC detecting. The reaction mixture was cooled to room temperature, quenched with saturated aqueous sodium bicarbonate solution, the aqueous phase was extracted with dichloromethane (3 mL3). The organic phase was washed with saturated brine, dried over anhydrous magnesium sulfate and allowed to stand. The desiccant was removed by suction filtration, and the filtrate was decanted by a rotary evaporator and the resulting crude product was used directly in the next step to replace the reaction.

[0080] To a dry 15 mL Schlenk tube equipped with a magnetic stirrer in a nitrogen atmosphere, was added the crude product obtained above, indium trichloride (139 mg, 0.63 mmol), 1,3-propanedithiol (39 mg, 0.36 mmol) and 3 mL of 1,2-dichloroethane. The reaction solution was heated to 85 C. for 2 hours by oil bath and the reaction was reacted complete and analyzed by TLC detecting. The reaction mixture was cooled to room temperature, quenched with 10% aqueous sodium hydroxide solution (2 mL). The aqueous phase was extracted with dichloromethane (3 mL3). The organic phase was washed with saturated brine, dried over anhydrous magnesium sulfate and allowed to stand. The desiccant was removed by suction filtration, and the filtrate was removed with a rotary evaporator. The residue was purified by silica gel column chromatography (petroleum ether:ethyl acetate=10:1) to give 86 mg of white solid with 52% yield.

[0081] Mp 62-64 C., [].sub.D.sup.25 274.8 (c 0.5, CHCl.sub.3). .sup.1H NMR (400 MHz, CDCl.sub.3) 7.31-6.93 (m, 15H), 6.67 (d, J=7.3 Hz, 1H), 5.98 (d, J=7.9 Hz, 1H), 3.75 (dd, J=7.4, 6.3 Hz, 1H), 3.30 (dd, J=6.6, 4.2 Hz, 1H), 3.11-2.96 (m, 5H), 2.76-2.38 (m, 7H), 2.34-2.26 (m, 1H), 2.18-2.10 (m, 1H), 2.02-1.92 (m, 1H), 1.82-1.70 (m, 1H). .sup.31P NMR (162 MHz, CDCl.sub.3) 22.4 (s). .sup.13C NMR (101 MHz, CDCl.sub.3) 153.3 (d, J=25.3 Hz), 144.6 (d, J=3.0 Hz), 144.4 (d, J=7.9 Hz), 142.7 (d, J=1.7 Hz), 139.8 (d, J=13.5 Hz), 136.8 (d, J=14.0 Hz), 134.5, 134.3, 134.1, 133.9, 133.4 (d, J=3.4 Hz), 133.1, 133.0, 128.4 (d, J=4.3 Hz), 128.1, 128.0, 128.0, 127.6 (d, J=8.7 Hz), 113.8, 107.9, 61.6 (d, J=3.1 Hz), 46.1, 45.3, 40.2 (d, J=5.3 Hz), 36.2, 31.5, 31.0, 28.6, 28.4, 25.9. HRMS (MALDI) Calcd for C.sub.34H.sub.35NPS.sub.2 [M+H].sup.+: 552.1943; Found: 552.1945.

Example 18

Application of Chiral Spiro Phosphine-Nitrogen-Sulfur Tridentate Ligand in the Asymmetric Catalytic Hydrogenation Reaction of Carbonyl Compounds

[0082] ##STR00024##

[0083] (R)-I or II (1.65 mol) and [Ir(COD)Cl].sub.2 (0.5 mg, 0.75 mol) were weighed in a glove box. Then it was sealed standby in a dry, clean 10 mL Schlenk tube with a magnetic stirrer. When taking out, 1 mL of anhydrous methanol was added and stirred at room temperature for 0.5 hour. Under nitrogen atmosphere, the solution was injected with a syringe to a hydrogenation reactor equipped with a glass inner tube and a magnetic stirrer. The gas in the autoclave was replaced three times with hydrogen to adjust the hydrogen pressure to 10 atm (ligand (R)-II, at that time the hydrogen pressure was adjusted to 30 atm). After stirring for 0.5 hour at room temperature, the hydrogen in the autoclave was slowly released. Under a nitrogen atmosphere, was injected to the reactor 7.5150 mmol substrate (after the solid substrate was dissolved in methanol) and 0.0525 mmol sodium hydroxide in methanol (0.5 mL (0.1 mmol/mL)-25 mL (1 mmol/mL)). Quickly replace the gas in the reactor with hydrogen three times, and finally adjust the hydrogen pressure to 810 atm, the reaction was stirred at room temperature until the hydrogen pressure is no longer reduced. Slowly release the hydrogen in the reactor, use rotary evaporator to remove the solvent from the crude product. After removal of the catalyst by a short silica gel column, the optical purity of the product was analyzed by gas chromatography or nuclear magnetic resonance analysis, and the results of the hydrogenation experiments are shown in Table 1.

TABLE-US-00001 TABLE 1 Asymmetric catalytic hydrogenation of carbonyl compounds Yield Number Carbonyl Compound I or II S/C Reaction time (h) (%) Ee (%) 1 [00025] (R)-Ia 1000 0.5 92 84 (R) 2 [00026] (R)-IIa 1000 0.5 92 95 (R) 3 [00027] (R)-IIa 100000 20 h 90 95 (R) 4 [00028] (R)-IIa 500000 72 68 93 (R) 5 [00029] (R)-IIa 1000 0.5 91 98 (R) 6 [00030] (R)-IIa 1000 4 94 98 (R) 7 [00031] (R)-IIa 1000 2 92 98 (R) 8 [00032] (R)-IIa 1000 2 98 98 (R) 9 [00033] (R)-IIa 1000 2 93 98 (S) 10 [00034] (R)-IIa 1000 3 96 99.9 (S) 11 [00035] (R)-IIa 1000 2 96 98 (R) 12 [00036] (R)-IIa 1000 2 98 99 (R) 13 [00037] (R)-IIa 50000 2 96 99 (R) 14 [00038] (R)-IIa 1000 2 95 98 (R) 15 [00039] (R)-IIa 1000 4 97 98 (S) 16 [00040] (R)-IIa 1000 0.5 92 99.9 (S) 17 [00041] (R)-IIa 1000 4 93 95 (S) 18 [00042] (R)-IIa 1000 3 96 99.9 (S) 19 [00043] (R)-IIa 1000 0.5 91 90 (S) 20 [00044] (R)-IIa 1000 8 98 87