3,3,3′,3′-tetramethyl-1,1′-spirobiindane-based phosphinooxazoline ligand compound, preparation method and uses of the same

Abstract

The invention discloses a tetramethyl-7,7′-spirobiindane-based phosphinooxazoline ligand compound and its preparation method and use. The phosphinooxazoline ligand compound is a compound having a structure shown in general formula I or an enantiomer, a raceme or a diastereoisomer thereof. The phosphinooxazoline ligand obtained through a series of reaction steps using cheap and easily available 3,3,3′,3′-tetramethyl-1,1′-spirobiindane-6,6′-diol as a starting material. The novel phosphinooxazoline ligand developed in the invention can be used to organic catalytic reactions, especially as a chiral phosphinooxazoline ligand widely used in metal-asymmetric catalytic reactions, having economical practicality and industrial application prospects. ##STR00001##

Claims

1. A 3,3,3′,3′-tetramethyl-1,1′-spirobiindane-based phosphinooxazoline ligand, being a enantiomer or a diastereoisomer of a compound represented by formula I: ##STR00035## wherein R.sup.1 and R.sup.6 are each independently selected from the group consisting of hydrogen, C.sub.1-C.sub.10 alkyl or perfluoroalkyl, C.sub.3-C.sub.6 cycloalkyl, and C.sub.1-C.sub.4 alkoxy or perfluoroalkoxy; R.sup.2, R.sup.3, R.sup.4, and R.sup.5 are each independently selected from the group consisting of hydrogen, halogen, C.sub.1-C.sub.10 alkyl or perfluoroalkyl, and C.sub.3-C.sub.6 cycloalkyl; R.sup.7 is selected from the group consisting of hydrogen, C.sub.1-C.sub.10 alkyl or perfluoroalkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.6-C.sub.14 aryl, CMe.sub.2OBn, CMe.sub.2Ph, CMePh.sub.2, CPh.sub.3, CH(Ph)OMe, and CH(Ph)OBn; R.sup.8 and R.sup.9 are each independently selected from the group consisting of hydrogen, C.sub.1-C.sub.10 alkyl or perfluoroalkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.6-C.sub.14 aryl, CH.sub.2OCHPh.sub.2, CH.sub.2OCPh.sub.3, and CH.sub.2OCH.sub.2Ph; and R.sup.10 is selected from the group consisting of C.sub.1-C.sub.10 alkyl or perfluoroalkyl, C.sub.3-C.sub.6 cycloalkyl, and C.sub.6-C.sub.14 aryl.

2. The 3,3,3′,3′-tetramethyl-1,1′-spirobiindane-based phosphinooxazoline ligand according to claim 1, wherein the compound represented by formula I is any one of the following compounds: ##STR00036## ##STR00037##

3. A preparation method of the compound I according to claim 1, comprising the following steps: preparing a compound represented by formula III through a mono-substitution reaction of a compound represented by formula II, as a starting material, with disubstituted phosphine halide under an effect of an alkali, subjecting the compound represented by formula III to a palladium-catalyzed cyanation, an acidic hydrolysis, and a condensation reaction with an aminoethanol compound to form amphenicol, and then conducting a cyclization reaction to obtain the compound represented by formula I, as the following reaction scheme: ##STR00038## ##STR00039## wherein R.sup.1-R.sup.10 in the formula I are the same as those defined in claim 1; X in the formula II is bromine or iodine; and wherein EDCI is 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, and HOBt is 1-hydroxylbenzotriazole.

Description

BRIEF DESCRIPTION OF DRAWINGS

(1) FIG. 1 is an X-ray crystal diffraction pattern of a product in Example 5 of the present application.

DESCRIPTION OF EMBODIMENTS

(2) The following examples are provided to facilitating the understanding of the present application, but are not intended to limit to the present application.

(3) General reaction conditions are described as below: when using air-sensitive reagents, all reactions and controls are performed in a nitrogen-filled glove box or using standard Schlenk technology. The reaction solvents are dried by a general standard process.

Example 1

Synthesis of 3,3,5,3′,3′,5′-hexamethyl-7-bromo-7′-(diphenylphosphino)-1,1′-spirobiindane (III-b)

(4) ##STR00011##

(5) Under nitrogen atmosphere, II-b (1 g, 1.08 mmol) and 15 mL of degassed anhydrous tetrahydrofuran were added to a reaction flask. The temperature was lowered to −78° C. An n-hexane solution of tert-butyllithium (1 mL, 0.6M) was added. After three hours of reaction, diphenylphosphine chloride (2 mmol) was added. After 30 minutes, the temperature naturally was raised to room temperature, and the reaction continued for 6 hours. An appropriate amount of dilute hydrochloric acid was added to quench and finish the reaction. Extraction was performed with ethyl acetate. The organic phase was washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, and filtered with suction. The filtrate was concentrated, and purified with silica gel flash column chromatography (eluent:petroleum ether:ethyl acetate=50:1) to obtain III-b, with a yield of 50%; m.p. 212-213° C.; .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.23-7.14 (m, 6H), 7.07-6.99 (m, 4H), 6.97 (s, 1H), 6.87 (s, 1H), 6.72 (d, J=4.6 Hz, 1H), 6.64 (s, 1H), 2.76 (d, J=11.9 Hz, 1H), 2.55 (d, J=13.1 Hz, 1H), 2.31 (d, J=13.1 Hz, 1H), 2.24 (d, J=5.8 Hz, 7H), 1.42 (s, 3H), 1.37 (s, 3H), 1.35 (s, 3H), 1.28 (s, 3H).

Example 2

Synthesis of (R)-3,3,5,3′,3′,5′-hexamethyl-7-bromo-7′-(diphenylphosphino)-1,1′-spirobiindane

(6) ##STR00012##

(7) Under nitrogen atmosphere, (R)-II-b (4.62 g, 10 mmol), diphenylphosphine oxide (4.02 g, 20 mmol), palladium acetate (224.5 mg, 1 mmol), 1,4-bis(diphenylphosphino) butane (dppb, 426.5 mg, 2 mmol), and 40 mL of fully degassed dimethyl sulfoxide DMSO were added in a dried reaction flask, and stirred to mix thoroughly. N, N-diisopropylethylamine (7.0 mL, 40 mmol) was added and heated to 100° C., and reacted for 24 hours. TLC was used to monitor the reaction. The solution was cooled to room temperature, diluted with ethyl acetate, and washed with saturated brine. The organic phase was washed sequentially with 5% HCl solution, saturated NaHCO.sub.3 solution, and saturated NaCl solution, dried over anhydrous Na.sub.2SO.sub.4, filtered to remove the solvent, and purified with flash chromatography on silica gel column (eluent: ethyl acetate/petroleum ether=1/4) to obtain 2.9 g of white solid product (R)-II-bb; m.p. 251-252° C.; H NMR (400 MHz, CDCl.sub.3) δ 7.46-7.27 (m, 10H), 7.12 (s, 1H), 6.87 (s, 1H), 6.80 (d, J=15.0 Hz, 1H), 6.27 (s, 1H), 3.45 (d, J=12.2 Hz, 1H), 2.48 (d, J=13.1 Hz, 1H), 2.24 (dd, J=20.6, 10.4 Hz, 8H), 1.63 (s, 3H), 1.40 (s, 3H), 1.35 (s, 3H), 1.27 (s, 3H); HRMS (GC-TOF, EI): calcd for C.sub.35H.sub.36OPBr 582.1687, found 582.1672.

(8) Under nitrogen atmosphere, (R)-II-bb (1.75 g, 3 mmol) and 20 mL of anhydrous ethylene glycol dimethyl ether (DME) were added to a reaction flask, and mixed under stirring. CF.sub.3SO.sub.3CH.sub.3 (375p, 3.3 mmol) was added at room temperature, and then stirred and reacted at room temperature for 3 hours. Subsequently, the reaction flask was placed in an ice water bath, LiAlH.sub.4 (3 ml, 7.5 mmol, 2.5 mol/L in THF) solution was slowly added dropwise, and then the mixture was naturally warmed to room temperature. Subsequently, the reaction was carried out at room temperature for 3 hours, and the reaction condition was monitored by using TLC. Then 1 M dilute HCl solution was slowly added dropwise in the ice bath to quench the reaction, followed by extraction with ethyl acetate. The organic phase was washed with saturated NaCl, dried over anhydrous Na.sub.2SO.sub.4, filtered to remove the solvent, and purified with silica gel flash column chromatography (eluent: ethyl acetate/petroleum ether=1/50) to obtain a white solid product (R)-III-b (1.6 g, yield 93%); .sup.31P NMR (162 MHz, CDCl.sub.3) δ −22.66; HRMS (GC-TOF): calcd for C.sub.35H.sub.36PBr 566.1738, found 566.1756.

Example 3

Synthesis of

(R)-3,3,5,3′,3′,5′-hexamethyl-7-bromo-7′-(bis(3,5-bis(trifluoromethyl)phenyl)phosphino)-1,1′-spirobiindane ((R)-III-b)

(9) ##STR00013##

(10) Under nitrogen atmosphere, (R)-II-b (1 mmol) and 15 mL of degassed anhydrous tetrahydrofuran were added into a reaction flask. The temperature was lowered to −78° C., and an n-hexane solution of t-butyllithium (1.1 mL, 1.6M) was added. After reacting for three hours, bis(3,5-bis(trifluoromethyl) phenyl)phosphine chloride (2 mmol) was added. The temperature naturally was raised to room temperature after 30 minutes, and the reaction continued for 6 hours. The reaction was quenched by adding an appropriate amount of dilute hydrochloric acid, followed by extracting with ethyl acetate. The organic phase was washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, and suction filtered. The filtrate was concentrated, and purified with silica gel flash column chromatography (eluent:petroleum ether:ethyl acetate=50:1) to obtain (R)-III-c, with a yield of 45%.

Example 4

Synthesis of 3,3,5,3′,3′,5′-hexamethyl-7′-(diphenylphosphino)-1,1′-spirobiindane-7-formic acid (V)

(11) ##STR00014##

(12) Under N.sub.2 protection, III-b (2.84 g, 5 mmol), Zn(CN).sub.2 (645.7 mg, 5.5 mmol) and Pd(PPh.sub.3 (577.8 mg, 0.5 mmol) were added into a 100 mL three-necked flask. 50 mL of anhydrous DMF was added, and under stirring, the temperature was raised to about 130° C. The reaction condition was monitored by TLC, and the reaction was completed and stopped after 36 h. The reaction system was cooled to room temperature, diluted with ethyl acetate, washed sequentially with saturated NaHCO.sub.3 and saturated NaCl, dried over anhydrous Na.sub.2SO.sub.4, and purified with silica gel column chromatography (eluent: ethyl acetate/petroleum ether=1/50) after removing the solvent through rotary evaporation to obtain a product of 3,3,5,3′,3′,5′-hexamethyl-7-cyano-7′-(diphenylphosphino)-1,1′-spirobiindane (IV), (1.67 g, yield 65%); m.p. 220-221° C.; .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.26 (dd, J=12.3, 4.6 Hz, 1H), 7.23-7.15 (m, 5H), 7.06 (s, 1H), 7.02 (s, 1H), 6.97 (td, J=9.2, 3.9 Hz, 4H), 6.69 (d, J=4.1 Hz, 1H), 6.41 (s, 1H), 3.06 (dd, J=13.1, 2.5 Hz, 1H), 2.44-2.39 (m, 1H), 2.36 (d, J=1.8 Hz, 2H), 2.23 (s, 3H), 2.20 (s, 3H), 1.55 (s, 3H), 1.47 (s, 3H), 1.36 (s, 3H), 1.29 (s, 3H).

(13) Under N.sub.2 protection, IV (1.03 g, 2 mmol) was added into a 100 mL three-necked flask, and then a degassed acid mixture solution of 10 ml H.sub.2SO.sub.4,15 ml H.sub.2O and 5 ml AcOH was added. The system was warmed up to about 145° C., and reacted under reflux with stirring, and the reaction condition was monitored by TLC. After 48 h, the reaction was completed and stopped, the temperature was cooled to room temperature, followed by diluting and quenching with water under an ice bath. Extraction was performed three times with ethyl acetate. The organic phase was washed with saturated NaCl, dried over anhydrous Na.sub.2SO.sub.4, and purified with silica gel column chromatography (eluent: ethyl acetate/petroleum ether=1/10) after removing the solvent through rotary evaporation, so as to obtain a product V, 0.80 g, with a yield of 75%; m.p. 237-238° C.; .sup.1H NMR (400 MHz, DMSO) δ 12.13 (s, 1H), 7.30 (d, J=6.5 Hz, 4H), 7.24-7.14 (m, 4H), 7.00-6.91 (m, 3H), 6.86 (dd, J=10.9, 4.1 Hz, 2H), 6.48 (d, J=4.0 Hz, 1H), 2.74 (d, J=12.3 Hz, 1H), 2.32 (s, 3H), 2.21 (s, 2H), 2.18-2.10 (m, 4H), 1.40 (s, 3H), 1.30 (s, 3H), 1.25 (s, 3H), 1.14 (s, 3H).

(14) According to the above reaction process, the chiral compound (R)-3,3,5,3′,3′,5′-hexamethyl-7′-(diphenylphosphino)-1,1′-spirobiindane-7-formic acid ((R)-V) was obtained by using the chiral compound (R)-III-b instead of III-b, and a yield of the two steps achieved 55%.

Example 5

Synthesis of 3,3,5,3′,3′,5′-hexamethyl-7′-(diphenylphosphino)-1,1′-spirobiindane-7-oxazoline

(15) ##STR00015##

(16) Under N.sub.2 protection, V (266.3 mg, 0.5 mmol), L-valinol (154.7 mg, 1.5 mmol), EDCI (287.6 mg, 1.5 mmol), and HOBt (202.7 mg, 1.5 mmol) were added into a 50 mL three-necked flask. 20 mL of anhydrous N,N-dimethylformamide (DMF) was added at room temperature to react under stirring, and the reaction condition was monitored by TLC. After 24 h, the reaction was complete. The reaction was stopped and quenched with water, followed by extracting with ethyl acetate, washing with saturated NaCl, drying over anhydrous Na.sub.2SO.sub.4, and filtering. The solvent was then removed from the filtrate by rotary evaporation, and a product VI-1 was obtained and used directly in a next step of reaction.

(17) Under N.sub.2 protection, VI-1 (0.5 mmol) and DMAP (6.1 mg, 0.05 mmol, 4-N-dimethylaminopyridine) were added into a 50 mL three-necked flask. 15 mL of anhydrous CH.sub.2Cl.sub.2 was added and dissolved under stirring. Then, Et.sub.3N (555 μL, 4 mmol) and MsCl (155 μL, 2 mmol) were added sequentially in ice-water bath. Then, the system was naturally warmed to room temperature and stirred overnight. The reaction condition was tracked by TLC until the reaction was complete. The system was quenched with water, extracted with CH.sub.2Cl.sub.2, washed with saturated NaCl, and dried over anhydrous Na.sub.2SO.sub.4. After removing solvent by rotary evaporation, the silica gel column chromatography (eluent: ethyl acetate/petroleum ether=1/20) was used for separation to obtain a pair of diastereoisomers (R.sub.a, S)-I-c (255 mg, with a yield of the two steps: 85%) and (S.sub.a, S)-I-c (234 mg, with a yield of the two steps: 78%).

(18) (R.sub.a, S)-I-c: m.p. 199-200° C.; [α].sub.D.sup.20=+131 (c 0.1, CH.sub.2Cl.sub.2); .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.39 (s, 1H), 7.22 (dd, J=6.8, 3.4 Hz, 3H), 7.20-7.16 (m, 3H), 7.09 (td, J=7.0, 3.1 Hz, 2H), 7.04 (s, 1H), 6.98-6.92 (m, 3H), 6.57 (d, J=4.4 Hz, 1H), 3.79-3.68 (m, 1H), 3.41 (dd, J=17.7, 9.6 Hz, 1H), 2.84 (t, J=9.2 Hz, 2H), 2.39 (s, 3H), 2.28-2.07 (m, 6H), 1.41 (s, 3H), 1.29 (s, 6H), 1.16-1.06 (m, 4H), 0.89 (d, J=6.6 Hz, 3H), 0.56 (d, J=6.7 Hz, 3H);

(19) (S.sub.a, S)-I-c: m.p. 190-191° C.; [α].sub.D.sup.20=−182 (c 0.1, CH.sub.2Cl.sub.2); .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.47 (s, 1H), 7.22 (dd, J=4.0, 2.3 Hz, 3H), 7.17 (d, J=4.6 Hz, 3H), 7.13-7.06 (m, 2H), 7.04 (s, 1H), 7.03-6.97 (m, 2H), 6.96 (s, 1H), 6.55 (d, J=4.5 Hz, 1H), 3.64-3.54 (m, 1H), 3.45 (dt, J=9.8, 6.3 Hz, 1H), 2.97 (dd, J=9.8, 8.2 Hz, 1H), 2.66 (d, J=12.6 Hz, 1H), 2.38 (s, 3H), 2.30-2.13 (m, 6H), 1.68 (dt, J=13.0, 6.7 Hz, 1H), 1.38 (s, 3H), 1.32 (s, 3H), 1.29 (s, 3H), 1.08 (s, 3H), 0.87 (d, J=6.8 Hz, 3H), 0.77 (d, J=6.8 Hz, 3H).

(20) According to the above experimental process, a single chiral ligand (R.sub.a, S)-I-c was obtained with a total yield of 90% by replacing the compound V with a chiral compound (R)-V.

(21) According to the above experimental process, different chiral amino alcohols are employed to prepare the following chiral phosphinooxazoline ligand compounds:

(S)-2-((R)-7′-(diphenylphosphanyl)-3,3,3′,3′,5,5′-hexamethyl-2,2′,3,3′-tetrahydro-1,1′-spirobi[inden]-7-yl)-4-phenyl-4,5-dihydrooxazole ((R.SUB.a., S)-I-2.11b)

(22) ##STR00016##

(23) 250 mg, a total two-step yield of 79%; white solid, m.p. 67-68° C.; [α].sub.D.sup.20=+74 (c 0.1, CH.sub.2Cl.sub.2); .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.57 (s, 1H), 7.24-7.19 (m, 3H), 7.13-6.94 (m, 11H), 6.90 (s, 1H), 6.73 (dd, J=8.0, 6.8 Hz, 3H), 4.83 (t, J=10.5 Hz, 1H), 4.21 (dd, J=9.9, 8.3 Hz, 1H), 3.14-2.87 (m, 2H), 2.41 (s, 3H), 2.27 (d, J=12.7 Hz, 2H), 2.19 (d, J=13.6 Hz, 1H), 2.08 (s, 3H), 1.37 (s, 3H), 1.32 (s, 3H), 1.30 (s, 3H), 1.13 (s, 3H);

(S)-2-((S)-7′-(diphenylphosphanyl)-3,3,3′,3′,5,5′-hexamethyl-2,2′,3,3′-tetrahydro-1,1′-spirobi[inden]-7-yl)-4-phenyl-4,5-dihydrooxazole ((S.SUB.a., S)-I-2.11b)

(24) ##STR00017##

(25) 238 mg, a total two-step yield of 75%; white solid, m.p. 38-39° C.; [α].sub.D.sup.20=−138 (c 0.1, CH.sub.2Cl.sub.2); .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.59 (s, 1H), 7.30-7.08 (m, 12H), 7.07-6.95 (m, 4H), 6.94 (s, 1H), 6.63 (d, J=2.3 Hz, 1H), 4.90-4.56 (m, 1H), 3.82-3.65 (m, 1H), 3.42-3.30 (m, 1H), 2.84-2.70 (m, 1H), 2.40 (s, 3H), 2.33-2.16 (m, 6H), 1.33 (d, J=6.0 Hz, 6H), 1.26 (s, 3H), 1.15 (s, 3H);

(S)-4-benzyl-2-((R)-7′-(diphenylphosphanyl)-3,3,3′,3′,5,5′-hexamethyl-2,2′,3,3′-tetrahydro-1,1′-spirobi[inden]-7-yl)-4,5-dihydrooxazole ((R.SUB.a., S)-I-2.11c)

(26) ##STR00018##

(27) 249 mg, a total two-step yield of 77%; white solid, m.p. 57-58° C.; [α].sub.D.sup.20=+106 (c 0.1, CH.sub.2Cl.sub.2); .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.46 (s, 1H), 7.23 (dd, J=7.0, 4.8 Hz, 5H), 7.17 (dd, J=7.4, 6.1 Hz, 6H), 7.07 (s, 1H), 6.97 (ddd, J=17.5, 11.6, 6.8 Hz, 5H), 6.64 (d, J=4.4 Hz, 1H), 4.10 (qd, J=9.3, 4.1 Hz, 1H), 3.75 (t, J=8.7 Hz, 1H), 3.04 (dd, J=13.7, 4.1 Hz, 1H), 2.89-2.71 (m, 2H), 2.41 (s, 3H), 2.25 (d, J=10.8 Hz, 4H), 2.20-2.06 (m, 2H), 1.73 (dd, J=13.6, 10.7 Hz, 1H), 1.37 (s, 3H), 1.31 (d, J=1.9 Hz, 6H), 1.08 (s, 3H);

(S)-benzyl-2-((S)-7′-(diphenylphosphanyl)-3,3,3′,3′,5,5′-hexamethyl-2,2′,3,3′-tetrahydro-1,1′-spirobi[inden]-7-yl)-4,5-dihydrooxazole ((S.SUB.a., S)-I-2.11c)

(28) ##STR00019##

(29) 246 mg, a total two-step yield of 76%; white solid, m.p. 61-62° C.; [α].sub.D.sup.20=−125 (c 0.1, CH.sub.2Cl.sub.2); .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.42 (s, 1H), 7.29-7.23 (m, 2H), 7.23-7.14 (m, 7H), 7.07 (dd, J=10.4, 3.3 Hz, 5H), 7.01-6.95 (m, 2H), 6.92 (s, 1H), 6.59 (d, J=3.9 Hz, 1H), 4.05-3.91 (m, 1H), 3.52 (dd, J=8.3, 6.2 Hz, 1H), 3.12 (t, J=8.8 Hz, 1H), 2.87 (dd, J=13.9, 4.3 Hz, 1H), 2.75 (d, J=12.5 Hz, 1H), 2.39 (s, 3H), 2.29-2.17 (m, 3H), 2.15 (s, 3H), 2.04 (dd, J=13.8, 10.2 Hz, 1H), 1.39 (s, 3H), 1.33 (s, 3H), 1.30 (s, 3H), 1.13 (s, 3H);

(4S,5S)-2-((R)-7′-(diphenylphosphanyl)-3,3,3′,3′,5,5′-hexamethyl-2,2′,3,3′-tetrahydro-1,1′-spirobi[inden]-7-yl)-4,5-diphenyl-4,5-dihydrooxazol ((R.SUB.a., S, S)-I-2.11d)

(30) ##STR00020##

(31) 259 mg, a total two-step yield of 73%; white solid, m.p. 213-214° C.; [α].sub.D.sup.20=+94 (c 0.1, CH.sub.2C.sub.2); H NMR (400 MHz, CDCl.sub.3) δ 7.71 (s, 1H), 7.25-7.18 (m, 6H), 7.11 (ddd, J=12.0, 7.4, 4.6 Hz, 5H), 7.05-6.90 (m, 8H), 6.87 (s, 1H), 6.81 (d, J=4.5 Hz, 1H), 6.64 (s, 1H), 6.62 (s, 1H), 4.62 (d, J=10.5 Hz, 1H), 4.14 (d, J=10.5 Hz, 1H), 3.03 (d, J=12.4 Hz, 1H), 2.45 (s, 3H), 2.29-2.16 (m, 3H), 2.10 (s, 3H), 1.33 (s, 3H), 1.22 (s, 3H), 1.13 (s, 3H), 1.00 (s, 3H);

(4,5S)-2-((S)-7′-(diphenylphosphanyl)-3,3,3′,3′5,5′-hexamethyl-2,2′,3,3′-tetrahydro-1,1′-spirobi[inden]-7-yl)-4,5-diphenyl-4,5-dihydrooxazole ((S.SUB.a., S, S)-I-2.11d)

(32) ##STR00021##

(33) 256 mg, a total two-step yield of 72%; white solid, m.p. 167-168° C.; [α].sub.D.sup.20=−43 (c 0.1, CH.sub.2Cl.sub.2); .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.54 (d, J=0.9 Hz, 1H), 7.25-7.05 (m, 15H), 6.97 (ddd, J=11.2, 7.9, 2.8 Hz, 4H), 6.77-6.53 (m, 4H), 4.85 (d, J=9.8 Hz, 1), 4.67 (d, J=9.8 Hz, 1H), 2.90 (d, J=12.5 Hz, 1H), 2.56 (d, J=12.9 Hz, 1H), 2.41 (d, J=12.4 Hz, 4), 2.18 (d, J=12.5 Hz, 1H), 2.07 (s, 3H), 1.32 (d, J=11.3 Hz, 9H), 1.13 (s, 3H).

(34) The single crystals were obtained by cultivation in isopropyl ether, and the results of X-ray diffraction analysis are as follows:

(35) The structure is shown in FIG. 1, and the data of crystal cell are as follows:

(36) Bond precision: C—C=0.0074 A Wavelength=1.54184

(37) Cell: a=11.6873(3)b=15.3134(3)c=14.6013(4) alpha-90 beta=110.631(3) gamma=90
Temperature: 293 K

(38) TABLE-US-00001 Calculated Reported Volume 2445.64(11) 2445.63(10) Space group P 21 P 1 21 1 Hall group P 2yb P 2yb Moiety 2(C50 H48 N O P), 2(C50 H48 N O P), formula C6 H14 O C6 H14 O

Example 6

(39) Application in Catalysts by Complexing with Metal Salts:

(40) A metal salt Cu(OTf).sub.2 (0.005 mmol) and the ligand (Ra, S)-I-2.11c (0.005 mmol) were added to a Schlenk tube under N.sub.2 protection. 1 ml of TFE (2,2,2-trifluoroethanol) was added and dissolved with stirring. The reaction was carried out under stirring at 50° C. for 60 min. Then, the solvent was removed under reduced pressure, and a quantitative metal complex [(R.sub.a, S)-I-2.11c]Cu(OTf).sub.2 was obtained after vacuum drying.

Example 7

(41) Application in Nickel-Assymetric Calculation of Sulfonamides

(42) ##STR00022##

(43) A metal salt Ni(ClO.sub.4).sub.2.6H.sub.2O (0.005 mmol) and the ligand (Ra, S, S)-I-2.11d (0.0075 mmol) were added to a Schlenk tube under N.sub.2 protection. 0.5 ml of TFE (2,2,2-trifluoroethanol) was added and dissolved under stirring, and a coordination reaction was carried out at 60° C. for 30 min. Subsequently, benzo[e][1,2,3]oxthiazine-2,2-dioxide derivative 3.1(0.1 mmol), arylboronic acid 3.2 (0.15 mmol) and 0.5 ml of a solvent TFE were added. Then, the reaction was carried out at 60° C. for 48 h. After the reaction is completed, the reaction solution was directly subjected to silica gel column chromatography (eluent: ethyl acetate/petroleum ether=1/20-1/8) to obtain a chiral product 33.

(44) The Results of Reactions are as Follows:

(R)-4-phenyl-3,4-dihydrobenzo[e][1,2,3]oxathiazine-2,2-dioxide (3.3a)

(45) ##STR00023##

(46) 23 mg, yield: 88%; m.p. 131-132° C.; 99% ee; HPLC analysis: Chiralpak IC-3 (hexane/i-PrOH=90/10, 220 nm, 1.0 mL/min), t.sub.R (major) 10.2 min, t.sub.R (minor) 11.7 min; [α].sub.D.sup.20=+28.2 (c 0.10, CH.sub.2Cl.sub.2); .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.44 (dd, J=6.5, 3.7 Hz, 3H), 7.39-7.29 (m, 3H), 7.10 (t, J=7.7 Hz, 2H), 6.83 (d, J=7.6 Hz, 1H), 5.91 (s, 1H), 4.70 (s, 1H);

(R)-4-(m-tolyl)-3,4-dihydrobenzo[e][1,2,3]oxathiazine-2,2-dioxide (3.3b)

(47) ##STR00024##

(48) 25 mg, yield: 91%; m.p. 83-84° C.; 99% ee; HPLC analysis: Chiralpak IC-3 (hexane/i-PrOH=95/5, 220 nm, 1.0 mL/min), t.sub.R (major) 15.0 min, t.sub.R (minor) 17.4 min; [α].sub.D.sup.20=+12.1 (c 0.31, CH.sub.2Cl.sub.2); .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.32 (dd, J=12.2, 4.8 Hz, 2H), 7.27-7.20 (m, 1H), 7.09 (ddd, J=15.0, 10.9, 2.6 Hz, 4H), 6.82 (d, J=7.8 Hz, 1H), 5.85 (s, 1H), 4.72 (s, 1H), 2.37 (s, 3H);

(R)-4-(p-tolyl)-3,4-dihydrobenzo[e][1,2,3]oxathiazine-2,2-dioxide (3.3c)

(49) ##STR00025##

(50) 24 mg, yield: 87%; m.p. 120-121° C.; 93% cc; HPLC analysis: Chiralpak IC-3 (hexane/i-PrOH=95/5, 220 nm, 1.0 mL/min), t.sub.R (major) 16.0 min, ta (minor) 17.4 min; [α].sub.D.sup.20=+18.7 (c 0.12, CH.sub.2Cl.sub.2); .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.31 (t, J=7.7 Hz, 1H), 7.27-7.17 (m, 4H), 7.07 (dd, J=15.6, 8.0 Hz, 2H), 6.82 (d, J=7.8 Hz, 1H), 5.86 (s, 1H), 4.73 (s, 1H), 2.38 (s, 3H);

(R)-4-([1,1′-biphenyl]-4-yl)-3,4-dihydrobenzo[e][1,2,3]oxathiazine-2,2-dioxide (3.3d)

(51) ##STR00026##

(52) 31 mg, yield: 92%; m.p. 167-168° C.; 99% ee; HPLC analysis: Chiralpak IC-3 (hexane/i-PrOH=90/10, 220 nm, 1.0 mL/min), t.sub.R (major) 12.5 min, t.sub.R (minor) 14.4 min; [α].sub.D.sup.20=+17.0 (c 0.10, CH.sub.2C.sub.2); .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.64 (d, J=8.2 Hz, 2H), 7.62-7.54 (m, 2H), 7.46 (dd, J=10.3, 4.7 Hz, 2H), 7.38 (ddd, J=24.0, 11.4, 6.0 Hz, 4H), 7.10 (dd, J=14.8, 7.9 Hz, 2H), 6.89 (d, J=7.7 Hz, 1H), 5.95 (d, J=8.5 Hz, 1H), 4.77 (d, J=8.4 Hz, 1H);

(S)-4-(2-chlorophenyl)-3,4-dihydrobenzo[e][1,2,3]oxathiazine-2,2-dioxide (3.3e)

(53) ##STR00027##

(54) 15 mg, yield: 51%; m.p. 114-115° C.; 93% ee; HPLC analysis: Chiralpak IF-3 (hexane/i-PrOH=90/10, 220 nm, 1.0 mL/min), t.sub.R (major) 6.2 min, t.sub.R (minor) 7.6 min; [α].sub.D.sup.20=+29.8 (c 0.08, CH.sub.2Cl.sub.2); .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.51-7.45 (m, 1H), 7.44-7.29 (m, 4H), 7.15-7.05 (m, 2H), 6.78 (d, J=7.7 Hz, 1H), 6.30 (s, 1H), 5.09 (s, 1H);

(R)-4-(3-chlorophenyl)-3,4-dihydrobenzo[e][1,2,3]oxathiazine-2,2-dioxide (3.31)

(55) ##STR00028##

(56) 27 mg, yield: 91%; m.p. 104-105° C.; 99% ee; HPLC analysis: Chiralpak IC-3 (hexane/i-PrOH=95/5, 220 nm, 1.0 mL/min), t.sub.R (minor) 8.8 min, t.sub.R (major) 11.5 min; [α].sub.D.sup.20=+16.6 (c 0.28, CH.sub.2C.sub.2); .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.45-7.32 (m, 4H), 7.28-7.23 (m, 1H), 7.11 (ddd, J=23.4, 11.7, 4.6 Hz, 2H), 6.83 (d, J=7.8 Hz, 1H), 5.87 (s, 1H), 4.79 (s, 1H);

(R)-4-(4-chlorophenyl)-3,4-dihydrobenzo[e][1,2,3]oxathiazine-2,2-dioxide (3.3 g)

(57) ##STR00029##

(58) 28 mg, yield: 93%; m.p. 139-140° C.; 99% ee; HPLC analysis: ChiralpakIC-3 (hexane/i-PrOH=90/10,220 nm, 1.0 mL/min), t.sub.R (major) 7.3 min, t.sub.R (minor) 9.8 min; [α].sub.D.sup.20=+8.5 (c 0.20, CH.sub.2C.sub.2); .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.45-7.27 (m, 5H), 7.15-7.03 (m, 2H), 6.80 (d, J=7.8 Hz, 1H), 5.88 (d, J=8.4 Hz, 1H), 4.86 (d, J=8.3 Hz, 1H);

(R)-4(4-(trifluoromethyl)phenyl)-3,4-dihydrobenzo[e][1,2,3]oxathiazin-2,2-dioxide (3.3h)

(59) ##STR00030##

(60) 25 mg, yield: 76%; m.p. 119-120° C.; 98% ee; HPLC analysis: Chiralpak IF-3 (hexane/i-PrOH=90/10, 220 nm, 0.8 mL/min), t.sub.R (minor) 5.9 min, t.sub.R (major) 6.8 min; [α].sub.D.sup.20=+34.3 (c 0.07, CH.sub.2Cl.sub.2); .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.64 (d, J=8.2 Hz, 2H), 7.43 (d, J=8.1 Hz, 2H), 7.30 (dd, J=11.5, 4.2 Hz, 1H), 7.12-7.00 (m, 2H), 6.73 (d, J=7.7 Hz, 1H), 5.91 (s, 1H), 4.72 (s, 1H);

(S)-4-(thiophen-3-yl)-3,4-dihydrobenzo[e][1,2,3]oxathiazine-2,2-dioxide (3.3i)

(61) ##STR00031##

(62) 22 mg, yield: 82%; white solid; m.p. 130-131° C.; 95% ee; HPLC analysis: Chiralpak IF-3 (hexane/i-PrOH=90/10,220 nm, 0.8 mL/min), ta (minor) 9.9 min, t.sub.R (major) 12.9 min; [α].sub.D.sup.20=+59.2 (c 0.07, CH.sub.2Cl.sub.2); .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.40 (ddd, J=4.3, 3.9, 2.3 Hz, 2H), 7.37-7.30 (m, 1H), 7.12 (td, J=7.7, 1.0 Hz, 1H), 7.05 (dd, J=8.3, 0.8 Hz, 1H), 7.01 (dd, J=4.9, 1.4 Hz, 1H), 6.94 (d, J=7.8 Hz, 1H), 6.04 (d, J=8.7 Hz, 1H), 4.79 (d, J=8.6 Hz, 1H);

(R)-4-(naphthalen-2-yl)-3,4-dihydrobenzo[e][1,2,3]oxathiazin-2,2-dioxide (3.3j)

(63) ##STR00032##

(64) 28 mg, yield: 90%; m.p. 138-139° C.; 98% ee; HPLC analysis: Chiralpak IC-3 (hexane/i-PrOH=90/10, 220 nm, 1.0 mL/min), ta (major) 11.4 min, t.sub.R (minor) 18.3 min; [α].sub.D.sup.20=−48.3 (c 0.10, CH.sub.2Cl.sub.2); .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.94-7.81 (m, 4H), 7.61-7.50 (m, 2H), 7.40-7.30 (m, 2H), 7.17-7.03 (m, 2H), 6.85 (d, J=7.8 Hz, 1H), 6.09 (d, J=11.3 Hz, 1H), 4.79 (s, 1H);

(R)-6-methyl-4-phenyl-3,4-dihydrobenzo[e][1,2,3]oxathiazine-2,2-dioxide (3.3k)

(65) ##STR00033##

(66) 26 mg, yield: 94%; m.p. 125-126° C.; 99% ee; HPLC analysis: Chiralpak IC-3 (hexane/i-PrOH=95/5, 220 nm, 1.0 mL/min), t.sub.R (major) 20.1 min, t.sub.R (minor) 21.9 min; [α].sub.D.sup.20=+57.0 (c 0.10, CH.sub.2C.sub.2); .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.49-7.42 (m, 1H), 7.39-7.31 (m, 1H), 7.12 (dd, J=8.4, 1.9 Hz, 1H), 6.97 (d, J=8.4 Hz, 1H), 6.60 (s, 1H), 5.86 (s, 1H), 4.65 (s, 1H), 2.21 (s, 1H);

(R)-6-chloro-4-phenyl-3,4-dihydrobenzo[e][1,2,3]oxathiazine-2,2-dioxide (3.31)

(67) ##STR00034##

(68) 26 mg, yield: 88%; m.p. 137-138° C.; 99% cc; HPLC analysis: Chiralpak IC-3 (hexane/i-PrOH=98/2, 220 nm, 0.8 mL/min), t.sub.R (major) 34.6 min, t.sub.R (minor) 40.7 min; [α].sub.D.sup.20=+33.9 (c 0.22, CH.sub.2Cl.sub.2); H NMR (400 MHz, CDCl.sub.3) δ 7.46 (d, J=2.9 Hz, 3H), 7.38-7.28 (m, 3H), 7.04 (d, J=8.8 Hz, 1H), 6.81 (d, J=1.3 Hz, 1H), 5.86 (s, 1H), 4.71 (s, 1H).

Example 8

(69) A metal salt Ni(ClO.sub.4).sub.2.6H.sub.2O (0.005 mmol) and the ligand (S.sub.a, S)-I-2.11b (0.005 mmol) were added into a Schlenk tube under N.sub.2 protection. Then, 0.5 ml of TFE (2,2,2-trifluoroethanol) was added and dissolved under stirring, and the reaction was carried out at 60° C. for 60 min. A metal complex [(S.sub.a, S)-I-2.11b]Ni(ClO.sub.4).sub.2 was obtained after vacuum drying.