3,3,3',3'-TETRAMETHYL-1,1'-SPIROBIINDANE-7,7'-DIOL

Abstract

Provided herein is 3,3,3′,3′-tetramethyl-1,1′-spirobiindane-7,7′-diol, which is a compound represented by formula I, or an enantiomer or a raceme thereof. The 3,3,3′,3′-tetramethyl-1,1′-spirobiindane-7,7′-diol is prepared with a 3,3,3′,3′-tetramethyl-1,1′-spirobiindane-7,7′-dicarbaldehyde derivative as a starting material through a Baeyer-Villiger oxidation rearrangement reaction and an alkaline hydrolysis reaction. The 3,3,3′,3′-tetramethyl-1,1′-spirobiindane-7,7′-diol comprises two gem-dimethyl groups and is a key intermediate for preparing corresponding 3,3,3′,3′-tetramethyl-1,1′-spirobiindane-based monophosphine ligands, such as phosphonite ligands, phosphite ligands, phosphoramidite ester ligands, phosphoric acid and phsophonamidate. The 3,3,3′,3′-tetramethyl-1,1′-spirobiindane-7,7′-diol skeleton provided herein could be used in chemical industry and has economic practicality and industrial application prospects.

##STR00001##

Claims

1. A 3,3,3′,3′-tetramethyl-1,1′-spirobiindane-7,7′-diol, being a compound represented by formula I, or an enantiomer thereof: ##STR00015## wherein R.sub.1 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.1-C.sub.4 alkoxy or perfluoroalkoxy, unsubstituted or substituted aryloxy, unsubstituted or substituted heteroaryloxy, unsubstituted or substituted arylmethyleneoxy, unsubstituted or substituted heteroarylmethyleneoxy, unsubstituted or substituted aryl, and unsubstituted or substituted heteroaryl; and R.sup.2 and R.sup.3 are each independently selected from the group consisting of hydrogen, halogen, C.sub.1-C.sub.10 alkyl or perfluoroalkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.1-C.sub.4 alkoxy or perfluoroalkoxy, unsubstituted or substituted aryloxy, unsubstituted or substituted heteroaryloxy, unsubstituted or substituted aryl, and unsubstituted or substituted heteroaryl; wherein the substituted aryloxy, the substituted aryl or the substituted heteroaryl has one or more substituents each independently selected from the group consisting of halogen, N-dimethylamino, C.sub.1-C.sub.4 alkyl or perfluoroalkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.1-C.sub.4 alkoxy or perfluoroalkoxy, methylenedioxy, aryl, aryloxy, and heteroaryl, and the heteroaryl is C.sub.5-C.sub.14 heteroaryl.

2. The 3,3,3′,3′-tetramethyl-1,1′-spirobiindane-7,7′-diol of claim 1, wherein the compound represented by formula I is any one of the following compounds, or an enantiomer or a raceme thereof: ##STR00016## ##STR00017##

Description

DETAILED DESCRIPTION OF THE EMBODIMENTS

[0015] The following examples are provided to facilitate understanding of the present application, but are not intended to limit the scope of the present application.

Example 1

[0016] ##STR00011##

[0017] To a three-necked flask, 2 g (6 mmol) of a III-a raceme compound was added, 150 mL of dichloromethane was added under nitrogen protection, the resulting mixture was cooled in an ice bath, and 0.9 mL of trifluoroacetic acid (12 mmol) was added, 4.28 g of m-chloroperoxybenzoic acid (m-CPBA, 27 mmol) was added in three batches, and then the resulting mixture was dissolved by stirring to obtain a reaction solution that was colorless and transparent. After stirring at room temperature overnight for 16 h, the reaction solution became light yellow. The reaction was monitored by a thin-layer chromatography (TLC) plate (color development with 2,4-dinitrophenylhydrazine) until the reaction was completed. 50 mL of saturated sodium sulfite solution was added to quench the reaction, and the organic phase was sequentially washed with water, saturated sodium bicarbonate solution, and saturated sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated to dryness under reduced pressure. The residual solid was dissolved with 10 mL of methanol, and 20 mL of 3 mol/L sodium hydroxide solution was slowly added thereto under stirring, and the resulting mixture was reacted overnight at room temperature. The reaction was monitored by a TLC plate. The reaction solution was acidified to be acidic using 3 mol/L hydrochloric acid at the end of the reaction, and a large amount of white solid precipitated. The resulting reaction solution was extracted with 20 mL of ethyl acetate, the organic phase was washed with saturated sodium chloride solution, and dried over anhydrous sodium sulfate, and the solvent was removed by rotary evaporation under reduced pressure. After purification with silica gel column chromatography (ethyl acetate/petroleum ether=1:10), 1.7 g of product II-a was obtained as a white solid (with a yield of 91%). IR(film): γ=3805, 3746, 3195, 2 983, 2925, 1748, 1683, 1585, 1469, 1456, 1360, 1304, 1242, 1201, 1175. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.21 (m, 2H), 6.83 (d, J=7.5 Hz, 2H), 6.66 (d, J=8.0 Hz, 2H), 4.43 (s, 2H), 2.39 (d, J=13.4 Hz, 2H), 2.33 (d, J=13.4 Hz, 2H), 1.41 (s, 6H), 1.36 (s, 6H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ154.08, 152.71, 130.36, 130.07, 115.41, 114.59, 77.37, 77.05, 76.74, 55.56, 54.14, 44.26, 31.94, 29.68. HRMS (EI, GC-TOF): caled for C.sub.21H.sub.24O.sub.2 308.1776, found: 308.1778.

[0018] Similarly, by replacing the III-a raceme compound with (R)-III-a compound, a (R)-II-a chiral compound could be obtained with a yield of 90%, [α].sup.20.sub.D=−130.1.

Example 2

[0019] ##STR00012##

[0020] To a three-necked flask, 1.44 g of (R)-III-b compound (4 mmol) was added, 150 mL of dichloromethane was added under nitrogen protection, the resulting mixture was cooled in an ice bath, and 3.2 g of m-CPBA (16 mmol) was added in three batches, 0.6 mL trifluoroacetic acid (8 mmol) was added, and then the resulting mixture was dissolved by stirring to obtain a reaction solution that was colorless and transparent. After stirring at room temperature overnight for 15 h, the reaction solution became light yellow. The reaction was monitored by a TLC plate (color development with 2, 4-dinitrophenylhydrazine) until the reaction was finished. 30 mL of saturated sodium sulfite solution was added to quench the reaction, and the organic phase was sequentially washed with water, saturated sodium bicarbonate, and saturated sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated to dryness under reduced pressure. The residual solid was dissolved with 40 mL of methanol, and 16 mL of 1 mol/L sodium hydroxide solution was slowly added thereto under stirring. The resulting mixture was reacted overnight at room temperature for 12 h, and the reaction was monitored by a TLC plate. The reaction solution was acidified to be acidic using 3 mol/L hydrochloric acid at the end of the solution, and a large amount of white solid precipitated. The resulting reaction solution was extracted with 100 mL of dichloromethane, the organic phase was washed with saturated sodium chloride solution, and dried over anhydrous sodium sulfate, and the solvent was removed by rotary evaporation under reduced pressure. After purification with silica gel column chromatography, 1.14 g of product (R)-II-b was obtained as a white solid (with a yield of 82%). Characterization data: m.p. 165-167° C.; [α]D.sup.20=−124.8 (c1.0, CH.sub.2Cl.sub.2); .sup.1H NMR (400 MHz, DMSO) δ6.63 (s, 2H), 6.50 (s, 2H), 4.41 (s, 2H), 2.35 (d, J=13.4 Hz, 2H), 2.30 (m, 8H), 1.38 (s, 6H), 1.33 (s, 6H); .sup.13C NMR (100 MHz, DMSO) δ154.0, 152.4, 140.7, 127.1, 116.1, 115.4, 55.9, 53.4, 44.1, 31.9, 29.6, 21.5.

[0021] Similarly, by replacing the (R)-III-b compound with the III-b raceme compound, the II-b raceme compound could be obtained with a yield of 80%.

Example 3

[0022] ##STR00013##

[0023] The product (R)-II-d was obtained (with a yield of 92%) according to the experimental procedure of Example 2 by replacing the (R)-III-b compound with (R)-III-d. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 6.55 (s, 2H), 5.09 (s, 2H), 3.71 (s, 6H), 2.47 (d, J=13.0 Hz, 2H), 2.29 (s, 6H), 2.22 (d, J=13.0 Hz, 2H), 1.37 (s, 6H), 1.31 (s, 6H).

Example 4

[0024] ##STR00014##

[0025] Under the protection of nitrogen, 20 mL of tetrahydrofuran, phosphorus trichloride (1.3 mmol) and triethylamine (2.7 mmol) were added sequentially to a dried round bottom flask. The resulting system was cooled to −78° C., stirred evenly, and 5 mL of II-b (1.25 mmol) solution in tetrahydrofuran was slowly injected thereto, and a large amount of white precipitate was quickly formed. After maintaining the temperature and reacting for 1 h, the temperature was naturally raised to room temperature, and the reaction was continued for 1 h to obtain a suspension. The suspension was filtered with a steel bridge under a condition free of water and oxygen, and the precipitate was removed and washed with 5 mL of tetrahydrofuran to obtain a clear solution of spirophosphinyl chloride. The clear solution was cooled to −78° C., and a solution of o-alkenylphenol lithium salt (ene-o) in THE was added therein, and the resulting mixture was reacted at this temperature for 1 h. Then the temperature was naturally raised to room temperature, and the reaction solution was stirred overnight, and then desolvated under reduced pressure. After purification with column chromatography, the compound I-bb was obtained as a white solid with a yield of 75%. Wherein, the solution of o-alkenylphenol lithium salt in THE was prepared as follows: under nitrogen protection, 5 mL tetrahydrofuran and o-alkenylphenol lithium salt (ene-o) (1.5 mmol) were added to a 10 mL reaction flask, and cooled to 30° C., and a solution of n-butyllithium (1.6 M, 1.5 mmol) in n-hexane was added thereto; the resulting mixture was reacted for 30 minutes at this temperature, then the temperature was naturally raised to room temperature and the solution of o-alkenylphenol lithium salt in THE was obtained.

[0026] Similarly, by replacing the II-b raceme compound with the (R)-II-b compound, the (R)-I-bb compound (which could be used as a chiral monophosphine ligand for metal-catalyzed asymmetric reactions) could be obtained with a yield of 70%. Characterization data: white solid, m.p. 60-62° C.; [α].sub.D.sup.20=+318 (c0.1, CH.sub.2Cl.sub.2); .sup.1H NMR (400 MHz, CDCl.sub.3) δ7.71-7.64 (m, 1H), 7.39 (d, J=7.3 Hz, 2H), 7.32 (t, J=7.5 Hz, 2H), 7.28-7.18 (m, 3H), 7.15-7.03 (m, 3H), 6.83 (s, 1H), 6.77 (s, 1H), 6.74 (s, 1H), 6.51 (s, 1H), 2.40 (dd, J=12.5, 10.4 Hz, 2H), 2.33 (s, 3H), 2.14-1.98 (m, 5H), 1.53 (s, 3H), 1.52 (s, 3H), 1.32 (s, 3H), 1.25 (s, 3H).