A process for the preparation of chiral alpha-boryl phosphonates

Abstract

The application relates to a preparation method of chiral alpha-boryl phosphate. Specifically, a diazophosphonate is used as a carbene source, a chiral oxazoline is used as a ligand, and a stable borane adduct is used in transition metal catalysis to perform a boron hydrogen insertion reaction to synthesize alpha-boryl phosphate with high corresponding selectivity. The synthesis method is simple in operation, and chiral alpha-boryl phosphate can be obtained in one step. The alpha-boryl phosphate can be converted into chiral alpha-hydroxyl phosphate through the functional group of a boron group, and has good application prospect.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, specifically relating to a method for synthesizing chiral α-boronyl phosphate compounds. Background Technology

[0002] Stabilized boranes have become very useful boron sources, widely used to introduce boron into the structure of organic molecules. Typical applications of stabilized boranes include their use as reducing agents to reduce unsaturated products and in boron-hydrogen insertion reactions with diazo compounds to rapidly construct various boron-containing compounds. Despite these important reactions, carbene sources are relatively limited, restricted to α-carbon carbenes and α-silyl carbenes. On the other hand, considering the importance of boron-containing compounds, the synthesis of chiral α-borane alkyl phosphates is of great significance. These α-borane alkyl phosphates can be synthesized into chiral α-hydroxyphosphates through the conversion of boron functional groups, showing promising applications. Summary of the Invention

[0003] The purpose of this invention is to overcome the shortcomings of the prior art and provide an efficient method for preparing chiral α-boronyl phosphates.

[0004] The technical solution of the present invention is as follows:

[0005] A method for synthesizing a chiral α-boronyl phosphate compound, comprising the following steps:

[0006] (1) Add chiral oxazoline and copper salt to a pressure-resistant sealed reaction vessel, remove air, fill with argon, add organic solvent, stabilize borane and diazonium phosphonate, stir the reaction at 20℃-40℃ for 12-36h, and use TLC to track the reaction to determine the specific time required for the reaction.

[0007] (2) Take the material obtained in step (1) out of the pressure-resistant sealed reaction vessel, cool it to room temperature, add ethyl acetate and mix thoroughly;

[0008] (3) The organic solvent in the organic phase obtained in step (2) is purified by silica gel column chromatography and then eluted with eluent to obtain the chiral α-boron alkyl phosphate compound.

[0009] In a preferred embodiment of the present invention, the chiral oxazoline is (3AR,3a'R,8aS,8a'S)-2,2'-(1,3-bis(4-(tert-butyl)phenyl)propane-2,2-diyl)bis(8,8a-dihydro-3aH-indeno[1,2-d]oxazole) (CAS: 2182671-16-3) or (3aS,3a'S,8aR,8a'R)-2,2'-(1,3-diphenylpropane-2,2-diyl)bis(3a,8a-dihydro-8H-indeno[1,2-d]oxazole) (CAS: 195703-68-5).

[0010] A further preferred chiral oxazoline is (3AR,3a'R,8aS,8a'S)-2,2'-(1,3-bis(4-(tert-butyl)phenyl)propane-2,2-diyl)bis(8,8a-dihydro-3aH-indeno[1,2-d]oxazol).

[0011] In a preferred embodiment of the present invention, the copper salt is one of copper tetraacetonitrile hexafluorophosphate, copper tetra(acetonitrile)tetrafluoroborate (I), and cuprous iodide.

[0012] A further preferred copper salt is copper tetraacetonitrile hexafluorophosphate.

[0013] In a preferred embodiment of the present invention, the organic solvent is one of cyclopentyl methyl ether, chlorobenzene, dichlorobenzene, dichloromethane, and chloroform.

[0014] A further preferred solvent is cyclopentyl methyl ether.

[0015] In a preferred embodiment of the present invention, the stabilized borane may be one of phosphoroborane, amineborane, and pyridineborane.

[0016] A further preferred stable borane is phosborane.

[0017] In a preferred embodiment of the present invention, the diazophosphonate is one of an aryl diazophosphate with no benzene ring substitution, a aryl diazophosphate with mono- or poly-substituted benzene ring.

[0018] In a preferred embodiment of the present invention, the eluent is a mixed solution of petroleum ether and ethyl acetate.

[0019] More preferably, the volume ratio of petroleum ether to ethyl acetate in the eluent is 1:1 to 3:1.

[0020] In a preferred embodiment of the present invention, in step (1), the ratio of stable borane, diazonium phosphonate, chiral oxazoline, copper salt, and organic solvent is 0.2 mmol: 0.2-0.4 mmol: 0.001 mmol: 0.0012 mmol, 1-2 mL.

[0021] In a preferred embodiment of the present invention, the reaction time is 12-15 hours.

[0022] The beneficial effects of this invention are:

[0023] 1. This invention enables the synthesis of chiral α-boronyl phosphate compounds with high enantioselectivity from stable boranes through atomic recombination using diazophosphonates as a carbene source under mild conditions and under argon protection.

[0024] 2. In line with the concept of green chemistry: The synthesis method of this invention uses copper, an inexpensive metal, as a catalyst, which is environmentally friendly.

[0025] 3. Simple operation: The synthesis method of the present invention is simple to operate and can obtain chiral α-boronyl phosphate in one step.

[0026] 4. The α-boronyl phosphate synthesized in this invention can be effectively converted into α-hydroxy phosphate, which has the effect of a herbicide. Detailed Implementation

[0027] To make the above-mentioned features and advantages of the present invention more apparent and understandable, specific embodiments are described below in detail. Unless otherwise specified, the methods of the present invention are conventional methods in the art.

[0028] Example 1:

[0029]

[0030] In air, 0.001 mmol of copper tetraacetonitrile hexafluorophosphate and 0.0012 mmol of (3AR,3a'R,8aS,8a'S)-2,2'-(1,3-bis(4-(tert-butyl)phenyl)propane-2,2-diyl)bis(8,8a-dihydro-3aH-indeno[1,2-d]oxazole) were added to a 25 mL pressure-resistant sealed reaction vessel. The mixture was evacuated and purged with argon gas, and the process was repeated three times. Then, under argon protection, 2 mL of cyclopentyl methyl ether (CPME), 0.2 mmol of dimethyl diazo(phenyl)methylphosphonate (substrate 1a), and 0.4 mmol of methyldiphenylphosphorane were added. The reaction mixture was stirred at 20 °C for 12–15 h, and the reaction time was monitored using TLC. After the reaction was complete, an appropriate amount of silica gel was added to the reaction mixture. After removing the solvent, the product was obtained by column chromatography with a volume ratio of petroleum ether to ethyl acetate of 1:1 to 1:3, with a yield of 86% and an ee value of 92%.

[0031] Among them, methyl diphenylphosphoronide is a publicly reported compound (5) Busacca, CA; Raju, R.; Grinberg, N.; Haddad, N.; James-Jones, P.; Lee, H.; Lorenz, JC; Saha, A.; Senanayake, CH J Org. Chem. 2008, 73, 1524-1531.

[0032] The universality of the substrates was studied under the standard conditions of this invention to demonstrate that the technical solution of this invention has good functional group compatibility. The substrate scope is as follows:

[0033]

[0034] All of the above substrates are publicly reported.

[0035] References:

[0036] (1) Ye, F.; Wang, C.; Zhang, Y.; Wang, J. Angew. Chem. Int. Ed. 2014, 53, 11625-11628.

[0037] (2)Zhou, Y.; Ye, F.; Zhou, Q.; Zhang, Y.; Wang, J. Org. Lett.2016,18,2024-2027.

[0038] (3) Sun, SM; Wei, YL; Xu, JXOrg. Lett. 2022, 24, 6024-6030.

[0039] (4) Zhou, Y.; Zhang, Y.; Wang, J. Org. Biomol. Chem. 2016, 14, 10444-10453.

[0040] Substrates 1a and 1f are reported in reference (1); substrates 1b, 1c, 1d, 1e, 1g, 1h, 1i, 1j, and 1l are reported in reference (2); substrates 1m, 1n, 1o, and 1p are reported in reference (3).

[0041] Substrate 1k reference (4) reported

[0042] The corresponding products are as follows:

[0043]

[0044] Example 2:

[0045]

[0046] In air, add 0.001 mmol of copper tetraacetonitrile hexafluorophosphate and 0.0012 mmol of (3AR,3a'R,8aS,8a'S)-2,2'-(1,3-bis(4-(tert-butyl)phenyl)propane-2,2-diyl)bis(8,8a-dihydro-3aH-indeno[1,2-d]oxazole) to a 25 mL pressure-resistant sealed reaction vessel. Evacuate the vessel and purge with argon, repeating the process three times. Then, under argon protection, add 2 mL of cyclopentyl methyl ether (CPME), 0.2 mmol of dimethyl diazophenyl methylphosphonate, and 0.4 mmol of stabilized borane (using ethyl diphenylphosphorane as an example). Stir the reaction mixture at 20 °C for 12–15 h, monitoring the reaction time using TLC. After the reaction is complete, add an appropriate amount of silica gel to the reaction mixture. After removing the solvent, the product was obtained by column chromatography with a volume ratio of petroleum ether to ethyl acetate of 1:1 to 1:3, with a yield of 77% and an ee value of 91%.

[0047] The substrate range is as follows:

[0048]

[0049] All of the above substrates are publicly reported.

[0050] References

[0051] (5) Busacca, CA; Raju, R.; Grinberg, N.; Haddad, N.; James-Jones, P.; Lee, H.; Lorenz, JC; Saha, A.; Senanayake, CHJOrg.Chem.2008,73,1524-1531.

[0052] (6) P.; Korzeniowska, E.; MJOrg.Chem.2017,82,10271-10296.

[0053] (7) Wang, C.;Ge, Q.;Xu, C.;Xing, Z.;Xiong, J.;Zheng, Y.;Duan, WLOrg. Lett. 2023, 25, 1583-1588.

[0054] (8)Lloyd-Jones, GC; Taylor, NPChem.-Eur.J.2015, 21, 5423-5428.

[0055] The reference for substrate 1q is (6).

[0056] The reference for substrate 1r is (7).

[0057] The reference for substrates 1s and 1t is (5).

[0058] The reference for substrate 1u is (8).

[0059] The corresponding products are as follows:

[0060]

[0061] Example 3:

[0062]

[0063] In air, 0.001 mmol of copper tetraacetonitrile hexafluorophosphate and 0.0012 mmol of (3AR,3a'R,8aS,8a'S)-2,2'-(1,3-bis(4-(tert-butyl)phenyl)propane-2,2-diyl)bis(8,8a-dihydro-3aH-indeno[1,2-d]oxazole) were added to a 25 mL pressure-resistant sealed reaction vessel. The mixture was evacuated and purged with argon gas, and the process was repeated three times. Then, under argon protection, 2 mL of cyclopentyl methyl ether (CPME), 0.2 mmol of dimethyl diazo(4-chlorophenyl)methylphosphonate, and 0.4 mmol of trimethoxyphosborane (substrate 1v) were added. The reaction mixture was stirred at 20 °C for 12–15 h, and the reaction time was monitored using TLC. After the reaction was complete, an appropriate amount of silica gel was added to the reaction mixture. After removing the solvent, the product was obtained by column chromatography with a volume ratio of petroleum ether to ethyl acetate of 1:1 to 1:3, with a yield of 62% and an ee value of 94%.

[0064] Dimethyl diazo(4-chlorophenyl)methylphosphonate is a publicly reported compound; see references.

[0065] Zhou, Y.; Ye, F.; Zhou, Q.; Zhang, Y.; Wang, J. Org. Lett. 2016, 18, 2024-2027. References for Trimethoxyphosborane

[0066] Paul, S.; Roy, S.; Monfregola, L.; Shang, S.; Shoemaker, R.; Caruthers, MHJAm.Chem.Soc.2015,137,3253-3264.

[0067] The substrate range is as follows:

[0068]

[0069] The corresponding products are as follows:

[0070]

[0071] Application Example 1: Preparation of (4-chlorophenyl)-hydroxyphosphoric acid

[0072]

[0073] 0.1 mmol of compound 22 prepared by the above method was dissolved in 0.5 mL of toluene, and 0.25 mL of 30 wt% hydrogen peroxide solution was added. The resulting mixture was heated to 65 °C and reacted for 12 h. After cooling to room temperature, the aqueous layer was extracted with ethyl acetate. The combined organic extracts were washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain the crude product. The crude product was then added to a reaction vessel containing 0.3 mL of 38% hydrochloric acid and reacted at 50 °C for 12 h. The mixture was extracted with dichloromethane, evaporated, and concentrated to obtain the corresponding α-hydroxyphosphoric acid (product 23) in 35% yield.

[0074]

[0075] In literature reports, compound 23 has been shown to inhibit p5C reductase. (See Forlani, G.; Occhipinti, A.; Berlicki, ...) ; G.; Wieczorek, A.; Kafarski, P. Tailoring the Structure of Aminobisphosphonates To Target Plant P5C Reductase. J. Agr. Food Chem. 2008, 56, 3193–3199.), can be applied to weed control.

[0076] The specific NMR data for the above products are as follows: 1

[0078] 1 H NMR(500MHz,Chloroform-d)δ7.52–7.46(m,3H),7.46–7.41(m,4H),7.41–7.38(m,1H), 7.35–7.30(m,2H),7.14–7.07(m,4H),7.05–7.00(m,1H),3.60(dd,J=14.9,10.5Hz,6H),

[0079] 13 C NMR(126MHz,Chloroform-d)δ141.5(dd,J=8.7,5.4Hz),131.8(dd,J=25.7,8.9Hz),131.1(dd,J=27.9,2.5Hz),129.7(d,J=58.1Hz),129.4(d,J =7.7Hz), 128.8 (dd, J = 30.4, 9.9Hz), 128.0 (d, J = 2.8Hz), 127.8 (d, J = 55.4Hz), 125.0 (d, J = 3.5Hz), 52.7 (dd, J = 66.7, 6.9Hz), 9.2 (d, J = 36.8Hz).

[0080] 11 B NMR(160MHz,Chloroform-d)δ-26.40.

[0081] 31 P NMR (202MHz, Chloroform-d) δ39.31 (d, J = 83.6Hz), 6.28. 2

[0083] 1H NMR(500MHz,Chloroform-d)δ7.51–7.45(m,2H),7.45–7.39(m,6H),7.36–7.31(m,2H),7.07–6.99(m,4H),3.60(dd,J=14.2,10.5Hz,6H),2.53–2.36(m,1H),1.44(d,J=10.2Hz,3H).

[0084] 13 C NMR(126MHz,Chloroform-d)δ140.2(dd,J=8.0,5.8Hz),131.7(dd,J=24.0,8.9Hz),131.2(dd,J=28.4,2.5Hz),130.6(d,J=7.7Hz),130.5(d,J=4.3Hz),129.4,128.8(dd,J=25.0,10.0Hz),127.9(d,J=2.9Hz),127.8(d,J=55.8Hz),52.7(dd,J=61.2,7.1Hz),9.5(d,J=37.3Hz).

[0085] 11 B NMR(160MHz,Chloroform-d)δ-26.85.

[0086] 31 P NMR(202MHz,Chloroform-d)δ38.54(d,J=81.0Hz),6.05. 3

[0088] 1 H NMR(400MHz,Chloroform-d)δ7.52–7.45(m,3H),7.45–7.38(m,5H),7.36–7.29(m,2H),7.09(s,4H),4.57(d,J=1.7Hz,2H),3.59(dd,J=17.0,10.6Hz,6H),2.52–2.37(m,1H),1.34(d,J=10.2Hz,3H).

[0089] 13C NMR(126MHz,Chloroform-d)δ137.9(d,J=3.1Hz),131.8(dd,J=24.6,8.9Hz),131.1(dd,J=30.7,2.0Hz),129.8,129.4(d,J=7.8Hz),128.8(dd,J=29.7,9.9Hz),128.1,127.6,126.8(d,J=2.6Hz),65.0,52.7(dd,J=52.7,6.8Hz),9.3(d,J=37.0Hz).

[0090] 11 B NMR(128MHz,Chloroform-d)δ-26.06.

[0091] 31 P NMR(162MHz,Chloroform-d)δ38.76(d,J=83.0Hz),5.55. 4

[0093] 1 H NMR(400MHz,Chloroform-d)δ7.51–7.45(m,3H),7.45–7.37(m,5H),7.36–7.28(m,2H),7.03(dd,J=8.6,2.6Hz,2H),6.65(d,J=8.3Hz,2H),3.72(s,3H),3.59(dd,J=15.1,10.5Hz,6H),2.46–2.30(m,1H),1.34(d,J=10.2Hz,3H).

[0094] 13 C NMR(101MHz,Chloroform-d)δ157.2(d,J=3.5Hz),133.1(dd,J=8.9,4.8Hz),131.8(dd,J=18.3,8.8Hz),131.1(dd,J=22.4,2.5Hz),130.2(d,J=7.6Hz),129.7(d,J=57.7Hz),128.7(dd,J=23.6,9.9Hz),127.9(d,J=55.6Hz),113.4(d,J=2.8Hz),55.1,52.6(dd,J=48.4,7.0Hz),9.4(d,J=36.9Hz).

[0095] 31 P NMR(162MHz,Chloroform-d)δ39.09(d,J=84.4Hz),5.76.

[0096] 11 B NMR(128MHz,Chloroform-d)δ-26.16. 5

[0098] 1 H NMR(500MHz,Chloroform-d)δ7.51–7.39(m,8H),7.35–7.30(m,2H),7.00(dd,J=8.1,2.4Hz,2H),6.90(d,J=7.7Hz,2H),3.60(dd,J=10.5,8.7Hz,6H),2.48–2.35(m,1H),2.24(s,3H),1.33(d,J=10.3Hz,3H).

[0099] 13 C NMR(126MHz,Chloroform-d)δ138.1(dd,J=8.3,5.7Hz),134.3(d,J=3.6Hz),131.8(dd,J=26.4,8.8Hz),131.0(d,J=32.2Hz),129.8(d,J=58.0Hz),129.2(d,J=7.6Hz),128.9(d,J=9.9Hz),128.7,128.6,128.0(d,J=55.2Hz),52.6(dd,J=64.8,6.8Hz),20.9,9.3(d,J=36.7Hz).

[0100] 11 B NMR(128MHz,Chloroform-d)δ-26.02.

[0101] 31 P NMR(202MHz,Chloroform-d)δ39.64(d,J=84.2Hz),6.39. 6

[0103] 1 H NMR(500MHz,Chloroform-d)δ7.89–7.84(m,2H),7.49–7.43(m,3H),7.43–7.37(m,5H),7.35–7.30(m,2H),7.25–7.20(m,2H),3.63(dd,J=10.6,6.2Hz,6H),2.67–2.54(m,1H),1.56(d,J=10.2Hz,3H).

[0104] 13C NMR(126MHz,Chloroform-d)δ150.8(dd,J=8.0,6.1Hz),145.3(d,J=3.6Hz),131.7(dd,J=15.5,9.0Hz),131.4(dd,J=21.4,2.5Hz),129.7(d,J=7.9Hz),128.9(dd,J=19.4,10.1Hz),128.4(d,J=58.2Hz),127.7(d,J=57.0Hz),123.1(d,J=2.4Hz),52.9(dd,J=55.4,7.0Hz),9.6(d,J=38.2Hz).

[0105] 11 B NMR(160MHz,Chloroform-d)δ-26.62.

[0106] 31 P NMR(202MHz,Chloroform-d)δ36.86(d,J=73.4Hz),5.50. 7

[0108] 1 H NMR(500MHz,Chloroform-d)δ7.77–7.72(m,2H),7.50–7.44(m,2H),7.43–7.37(m,6H),7.33–7.28(m,2H),7.16(dd,J=8.4,2.3Hz,2H),3.85(d,J=1.2Hz,3H),3.62–3.55(m,6H),2.59–2.46(m,1H),1.35(d,J=10.2Hz,3H).

[0109] 13 C NMR(126MHz,Chloroform-d)δ167.2,147.8(dd,J=8.1,5.5Hz),131.7(dd,J=23.7,8.9Hz),131.2(dd),129.2,129.2,128.8(dd,J=30.0,9.9Hz),127.5(d,J=56.0Hz),126.7(d,J=3.4Hz),52.7(dd,J=64.3,7.0Hz),51.8,9.4(d,J=37.4Hz).

[0110] 11 B NMR(160MHz,Chloroform-d)δ-26.79.

[0111] 31P NMR(202MHz,Chloroform-d)δ37.99(d,J=80.3Hz),5.89. 8

[0113] 1 H NMR(400MHz,Chloroform-d)δ7.55–7.45(m,3H),7.45–7.38(m,5H),7.37–7.30(m,2H),7.11–7.03(m,2H),6.76(t,J=8.6Hz,2H),3.66–3.53(m,6H),2.52–2.35(m,1H),1.40(d,J=10.2Hz,3H).

[0114] 13 C NMR(101MHz,Chloroform-d)δ160.7(dd,J=242.9,3.8Hz),137.0,131.8(d,J=9.0Hz),131.7(d,J=8.9Hz),131.3(d,J=2.5Hz),130.6(d,J=15.3Hz),130.6,128.8(dd,J=21.3,10.1Hz),128.6(dd,J=148.0,56.7Hz),114.7(d,J=2.8Hz),114.5(d,J=2.7Hz),52.7(dd,J=47.4,7.0Hz),9.5(d,J=37.3Hz).

[0115] 11 B NMR(128MHz,Chloroform-d)δ-25.98.

[0116] 31 P NMR(162MHz,Chloroform-d)δ38.37(dd,J=82.2,5.7Hz),5.50.

[0117] 19 F NMR(376MHz,Chloroform-d)δ-118.73(t,J=4.6Hz). 9

[0119] 1H NMR(500MHz,Chloroform-d)δ7.51–7.44(m,2H),7.44–7.38(m,6H),7.36–7.31(m,2H),7.17–7.13(m,2H),7.00–6.96(m,2H),3.60(dd,J=13.6,10.5Hz,6H),2.48–2.36(m,1H),1.45(d,J=10.2Hz,3H).

[0120] 13 C NMR(126MHz,Chloroform-d)δ140.7(dd,J=9.0,5.5Hz),131.7(dd,J=24.9,9.0Hz),131.3(d,J=2.6Hz),131.1,131.0(d,J=5.3Hz),130.9(d,J=2.8Hz),128.8(dd,J=23.7,10.0Hz),128.4(dd,J=162.0,57.2Hz),118.6(d,J=4.4Hz),52.7(dd,J=61.1,7.0Hz),9.5(d,J=37.3Hz).

[0121] 11 B NMR(160MHz,Chloroform-d)δ-26.68.

[0122] 31 P NMR(202MHz,Chloroform-d)δ38.33(d,J=78.7Hz),5.98. 10

[0124] 1 H NMR(400MHz,Chloroform-d)δ7.54(d,J=7.6Hz,2H),7.51–7.44(m,4H),7.44–7.37(m,6H),7.37–7.25(m,5H),7.19(dd,J=8.3,2.5Hz,2H),3.64(t,J=9.9Hz,6H),2.62–2.45(m,1H),1.43(d,J=10.2Hz,3H).

[0125] 13C NMR(101MHz,Chloroform-d)δ141.0(d,J=1.5Hz),140.7(dd,J=8.3,5.8Hz),137.6(d,J=3.7Hz),131.8(dd,J=23.1,8.9Hz),131.0(dd,J=25.6,2.5Hz),129.7(d,J=7.8Hz),129.2,128.7(dd,J=21.0,10.0Hz),128.6,128.0(d,J=55.7Hz),126.7,126.7,126.5(d,J=2.9Hz),52.7(dd,J=48.9,7.0Hz),9.4(d,J=37.0Hz).

[0126] 11 B NMR(128MHz,Chloroform-d)δ-25.86.

[0127] 31 P NMR(162MHz,Chloroform-d)δ38.54(d,J=81.9Hz),5.57. 11

[0129] 1 H NMR(500MHz,Chloroform-d)δ7.51–7.46(m,1H),7.46–7.37(m,7H),7.36–7.32(m,2H),7.30(d,J=8.0Hz,2H),7.18(dd,J=8.3,2.3Hz,2H),3.61(t,J=9.6Hz,6H),2.59–2.46(m,1H),1.52(d,J=10.2Hz,3H).

[0130] 13 C NMR(126MHz,Chloroform-d)δ148.2(d,J=7.3Hz),131.7(d,J=8.8Hz),131.6(d,J=8.9Hz),131.3(dd,J=21.5,2.5Hz),129.9(d,J=7.7Hz),128.9(dd,J=19.0,10.0Hz),128.1(dd,J=102.2,57.6Hz),119.3,108.3,52.8(dd,J=55.3,6.9Hz),9.5(d,J=38.0Hz).

[0131] 31 P NMR(202MHz,Chloroform-d)δ37.21(d,J=75.1Hz),5.60.

[0132] 11 B NMR(128MHz,Chloroform-d)δ-26.18. 12

[0134] 1 H NMR(400MHz,Chloroform-d)δ7.51–7.47(m,2H),7.47–7.42(m,4H),7.42–7.38(m,2H),7.36–7.30(m,2H),7.01(t,J=8.1Hz,1H),6.72–6.67(m,2H),6.61–6.55(m,1H),3.68(s,3H),3.62(t,J=10.6Hz,6H),2.54–2.36(m,1H),1.35(d,J=10.3Hz,3H).

[0135] 13 C NMR(101MHz,Chloroform-d)δ159.2(d,J=2.7Hz),142.7(dd,J=8.7,5.1Hz),131.8(dd,J=24.5,8.9Hz),131.2(dd,J=24.8,2.5Hz),129.6(d,J=57.5Hz),128.8(d,J=2.6Hz),128.8(dd,J=25.4,10.0Hz),127.8(d,J=55.4Hz),121.9(d,J=8.0Hz),114.7(d,J=7.7Hz),111.1(d,J=3.4Hz),55.0,52.9(dd,J=48.8,7.1Hz),9.3(d,J=37.0Hz).

[0136] 11 B NMR(128MHz,Chloroform-d)δ-26.15.

[0137] 31 P NMR(162MHz,Chloroform-d)δ38.78(d,J=84.8Hz),5.54. 13

[0139] 1H NMR(500MHz,Chloroform-d)δ7.65–7.60(m,1H),7.50–7.44(m,2H),7.44–7.40(m,2H),7.40–7.34(m,4H),7.31–7.26(m,2H),6.94–6.87(m,2H),6.75–6.64(m,1H),3.59(dd,J=10.5,6.5Hz,6H),3.03–2.89(m,1H),1.58(d,J=10.2Hz,3H).

[0140] 13 C NMR(101MHz,Chloroform-d)δ160.7(d,J=9.7Hz),158.3(d,J=9.9Hz),131.7(dd,J=11.9,9.0Hz),131.0(dd,J=18.7,2.5Hz),128.9,128.7(dd,J=18.0,10.0Hz),128.2(d,J=14.4Hz),126.1(dd,J=8.2,3.5Hz),123.7(t,J=3.5Hz),114.2(dd,J=23.6,2.6Hz),52.6(dd,J=44.9,6.9Hz),9.0(d,J=37.5Hz).

[0141] 11 B NMR(160MHz,Chloroform-d)δ-26.96.

[0142] 31 P NMR(202MHz,Chloroform-d)δ38.75(d,J=80.8Hz),5.78. 14

[0144] 1 H NMR(400MHz,Chloroform-d)δ7.94(dd,J=7.3,3.7Hz,1H),7.74(d,J=8.2Hz,1H),7.61–7.52(m,2H),7.48–7.42(m,1H),7.41–7.32(m,6H),7.32–7.24(m,5H),7.19(t,J=7.7Hz,1H),3.56(dd,J=38.8,10.5Hz,6H),3.45–3.31(m,1H),1.20(d,J=10.1Hz,3H).

[0145] 13C NMR(101MHz,Chloroform-d)δ137.3(dd,J=8.0,5.6Hz),133.7(d,J=2.0Hz),131.6(dd,J=17.3,8.9Hz),131.0(dd,J=15.8,2.5Hz),129.4(d,J=57.6Hz),128.6(dd,J=24.0,9.9Hz),127.8(d,J=55.5Hz),127.7(d,J=6.6Hz),125.5(d,J=4.2Hz),125.4(d,J=4.1Hz),125.1,124.7,123.1,52.7(dd,J=51.3,7.0Hz),9.3(d,J=36.7Hz).

[0146] 11 B NMR(128MHz,Chloroform-d)δ-25.28.

[0147] 31 P NMR(162MHz,Chloroform-d)δ38.94(d,J=80.9Hz),5.17. 15

[0149] 1 H NMR(500MHz,Chloroform-d)δ7.53–7.37(m,8H),7.32(t,J=7.5Hz,2H),7.12(d,J=7.0Hz,2H),7.08(t,J=7.3Hz,2H),7.00(t,J=7.2Hz,1H),4.04–3.80(m,4H),2.39(dd,J=21.0,9.3Hz,1H),1.30(d,J=10.2Hz,3H),1.17(t,J=6.9Hz,3H),1.11(t,J=7.0Hz,3H).

[0150] 13 C NMR(101MHz,Chloroform-d)δ141.8(dd,J=8.4,5.6Hz),131.8(dd,J=20.9,8.8Hz),131.0(dd,J=21.6,2.5Hz),130.1,129.5(d,J=7.8Hz),128.7(dd,J=22.7,9.9Hz),127.9(d,J=54.8Hz),127.8(d,J=2.8Hz),124.8(d,J=3.4Hz),61.4(dd,J=61.0,6.9Hz),16.3(t,J=5.7Hz),9.3(d,J=36.6Hz).

[0151] 11 B NMR(160MHz,Chloroform-d)δ-26.75.

[0152] 31 P NMR(202MHz,Chloroform-d)δ36.86(d,J=82.3Hz),6.44. 16

[0154] 1 H NMR(400MHz,Chloroform-d)δ7.51–7.44(m,4H),7.44–7.36(m,4H),7.35–7.28(m,2H),7.11(dd,J=7.4,2.4Hz,2H),7.06(t,J=7.4Hz,2H),6.98(dd,J=8.3,6.1Hz,1H),4.68–4.42(m,2H),2.41–2.24(m,1H),1.29(d,J=10.2Hz,3H),1.23–1.15(m,9H),0.89(d,J=6.2Hz,3H).

[0155] 13 C NMR(101MHz,Chloroform-d)δ142.5(dd,J=8.3,4.9Hz),131.8(dd,J=20.3,8.9Hz),131.0(dd,J=20.5,2.5Hz),130.0(d,J=58.9Hz),129.6(d,J=7.9Hz),128.7(dd,J=21.8,9.9Hz),128.1(d,J=54.4Hz),127.6(d,J=2.7Hz),124.6(d,J=3.4Hz),69.3(dd,J=64.5,7.3Hz),24.3(d,J=2.9Hz),24.1(d,J=3.2Hz),23.9(d,J=5.6Hz),23.3(d,J=5.8Hz),9.3(d,J=36.3Hz).

[0156] 11 B NMR(128MHz,Chloroform-d)δ-25.90.

[0157] 31 P NMR(162MHz,Chloroform-d)δ34.57(d,J=85.4Hz),6.20. 32 17

[0160] 1 H NMR(400MHz,Chloroform-d)δ7.51–7.43(m,3H),7.43–7.36(m,5H),7.36–7.30(m,2H),7.13–7.05(m,4H),7.04–6.97(m,1H),3.57(dd,J=21.1,10.4Hz,6H),2.39–2.23(m,2H),1.90(tq,J=14.5,7.5Hz,1H),1.36(dp,J=15.3,7.7Hz,1H),0.79(dt,J=17.2,7.5Hz,3H).

[0161] 13 C NMR(101MHz,Chloroform-d)δ141.4(dd,J=8.8,4.7Hz),132.4(dd,J=34.0,8.2Hz),131.0(d,J=2.1Hz),129.3(d,J=7.9Hz),128.6(dd,J=18.4,9.6Hz),128.1,127.8(d,J=2.9Hz),127.3(d,J=54.0Hz),125.0(d,J=3.5Hz),52.6(dd,J=43.5,7.0Hz),16.0(d,J=34.4Hz),6.6.

[0162] 11 B NMR(128MHz,Chloroform-d)δ-27.98.

[0163] 31 P NMR(162MHz,Chloroform-d)δ38.90(d,J=84.3Hz),14.17. 18

[0165] 1 H NMR(400MHz,Chloroform-d)δ7.56–7.44(m,4H),7.46–7.41(m,1H),7.43–7.32(m,6H),7.13–7.09(m,2H),7.06(t,J=7.6Hz,3H),7.01–6.95(m,1H),3.51(dd,J=21.4,10.4Hz,6H),2.25–2.10(m,2H),0.98(dd,J=14.5,7.0Hz,3H),0.89(dd,J=15.9,7.0Hz,3H).

[0166] 13C NMR(101MHz,Chloroform-d)δ139.9(dd,J=8.7,3.9Hz),133.5(dd,J=43.2,7.8Hz),131.0(dd,J=18.0,2.5Hz),129.6(d,J=7.7Hz),128.4(dd,J=9.5,2.8Hz),127.7(d,J=2.9Hz),125.3(d,J=16.0Hz),124.9,124.8(d,J=10.5Hz),52.6(dd,J=44.3,7.1Hz),22.5(d,J=32.2Hz),16.8(d,J=2.9Hz),16.7.

[0167] 11 B NMR(128MHz,Chloroform-d)δ-26.75.

[0168] 31 P NMR(162MHz,Chloroform-d)δ39.07(d,J=81.2Hz),25.28. 19

[0170] 1 H NMR(500MHz,Chloroform-d)δ7.52–7.43(m,3H),7.42–7.37(m,2H),7.21–7.16(m,2H),7.12(t,J=7.5Hz,2H),7.06–7.00(m,1H),3.62–3.56(m,6H),2.55–2.43(m,1H),1.29(d,J=10.7Hz,3H),1.17(d,J=10.5Hz,3H).

[0171] 13 C NMR(126MHz,Chloroform-d)δ141.6,131.0,130.5(d,J=8.6Hz),129.2(d,J=7.8Hz),129.2(d,J=54.8Hz),128.8(d,J=9.7Hz),128.0(d,J=2.7Hz),125.0(d,J=3.4Hz),52.6(d,J=62.8Hz),11.5(d,J=39.2Hz),9.5(d,J=37.2Hz).

[0172] 11 B NMR(202MHz,Chloroform-d)δ39.27(d,J=77.6Hz),-0.42.

[0173] 31 P NMR(160MHz,Chloroform-d)δ-26.66(d,J=168.2Hz). 20

[0175] 1 H NMR(500MHz,Chloroform-d)δ7.52–7.44(m,3H),7.44–7.38(m,2H),7.21–7.17(m,2H),7.12(t,J=7.4Hz,2H),7.06–7.01(m,1H),3.60(dd,J=17.5,10.5Hz,6H),2.49–2.37(m,1H),1.78–1.64(m,2H),1.56–1.45(m,1H),1.41–1.32(m,1H),0.95–0.87(m,3H),0.87–0.78(m,3H).

[0176] 13 C NMR(126MHz,Chloroform-d)δ141.9(dd,J=41.1,8.2,5.1Hz),131.7(d,J=7.4Hz),131.0(d,J=2.5Hz),129.2(d,J=7.9Hz),128.7(d,J=9.1Hz),127.9(d,J=2.7Hz),126.0(d,J=51.6Hz),52.7(dd,J=62.9,6.8Hz),15.8(d,J=35.7Hz),14.0(d,J=34.4Hz),6.5(d,J=2.4Hz),6.4(d,J=3.6Hz).

[0177] 11 B NMR(128MHz,Chloroform-d)δ-28.62(t,J=73.4,1.3Hz).

[0178] 31 P NMR(202MHz,Chloroform-d)δ39.57(d,J=77.7Hz),14.88. 21

[0180] 1 H NMR(400MHz,Chloroform-d) 1H NMR(400MHz,Chloroform-d)δ7.61–7.53(m,2H),7.47–7.40(m,1H),7.39–7.32(m,4H),7.17(t,J=7.5Hz,2H),7.10–7.01(m,1H),3.61(dd,J=47.0,10.4Hz,6H),2.72–2.55(m,1H),2.16–2.04(m,1H),1.87–1.74(m,2H),1.72–1.58(m,6H),1.56–1.43(m,3H),1.29–1.03(m,7H),0.94–0.84(m,2H),0.79–0.65(m,1H).

[0181] 13 C NMR(101MHz,Chloroform-d)δ142.1(d,J=7.8Hz),133.3(d,J=6.6Hz),130.8(d,J=2.5Hz),130.0(d,J=7.6Hz),128.3(d,J=9.0Hz),127.8(d,J=3.2Hz),124.9(d,J=3.9Hz),124.0(d,J=49.0Hz),52.8(dd,J=49.6,7.1Hz),30.9(dd,J=30.9,20.4Hz),26.9(d,J=39.0Hz),26.9(d,J=18.1Hz),26.8(d,J=2.6Hz),26.7,26.5,26.4,26.2(d,J=4.4Hz),25.7(d,J=8.4Hz).

[0182] 31 P NMR(162 MHz,Chloroform-d)δ39.12(d,J=78.9Hz),16.91.

[0183] 11 B NMR(128MHz,Chloroform-d)δ-29.53. 22

[0185] 1 H NMR(500MHz,Chloroform-d)δ7.27–7.23(m,2H),7.16(d,J=7.7Hz,2H),3.65(d,J=10.6Hz,3H),3.57(d,J=10.4Hz,3H),3.52(d,J=10.6Hz,9H),2.56–2.42(m,1H).

[0186] 31 P NMR (202MHz, Chloroform-d) δ 105.55, 38.63 (d, J = 101.3Hz).

[0187] 31 B NMR (160MHz, Chloroform-d) δ-32.73 (dd, J = 188.6, 105.6Hz). twenty three

[0189] 1 ¹H NMR (500MHz, Deuterium Oxide) δ 7.37 (s, 4H), 4.92 (d, J = 12.4Hz, 1H). The above description is only a preferred embodiment of the present invention, and therefore should not be construed as limiting the scope of the present invention. All equivalent changes and modifications made in accordance with the scope of the patent and the contents of the specification should still be covered by the present invention.

Claims

1. A process for the preparation of chiral α-borono phosphonates, characterized in that, Includes the following steps: (1) Add chiral oxazoline and copper salt to a pressure-resistant sealed reaction vessel, remove air, fill with argon, add organic solvent, stabilize borane and diazonium phosphonate, stir at 20℃-40℃ for 12-36 h, and use TLC to track the reaction to determine the specific time required for the reaction. (2) Take the material obtained in step (1) out of the pressure-resistant sealed reaction vessel, cool it to room temperature, add ethyl acetate and mix thoroughly; (3) The organic solvent in the organic phase obtained in step (2) was evaporated, purified by silica gel column chromatography, and then eluted with eluent to obtain the chiral α-boron alkyl phosphonate compound; The chiral oxazoline is (3AR,3a'R,8aS,8a'S)-2,2'-(1,3-bis(4-(tert-butyl)phenyl)propane-2,2-diyl)bis(8,8a-dihydro-3aH-indeno[1,2-d]oxazole) or (3aS,3a'S,8aR,8a'R)-2,2'-(1,3-diphenylpropane-2,2-diyl)bis(3a,8a-dihydro-8H-indeno[1,2-d]oxazole); The stabilized boronane is a phosborane; The diazophosphonate is an aryl diazophosphonate with no substitution on the benzene ring, a monosubstituted benzene ring, or a polysubstituted benzene ring.

2. The method according to claim 1, characterized in that, The copper salt is one of copper hexafluorophosphonate tetraacetonitrile, copper tetra(acetonitrile)tetrafluoroborate (I), and cuprous iodide.

3. The method according to claim 1, characterized in that, The organic solvent is one of cyclopentyl methyl ether, chlorobenzene, dichlorobenzene, dichloromethane, and chloroform.

4. The method according to claim 1, characterized in that, The eluent is a mixed solution of petroleum ether and ethyl acetate.

5. The method according to claim 4, characterized in that, The volume ratio of petroleum ether to ethyl acetate in the eluent is 1:1 to 3:

1.

6. The method according to claim 1, characterized in that, In step (1), the ratio of stable borane, diazonium phosphonate, chiral oxazoline, copper salt, and organic solvent is 0.2 mmol: 0.2-0.4 mmol: 0.001 mmol: 0.0012 mmol: 1-2 mL.

7. The method according to claim 1, characterized in that, The reaction time in step (1) is 12-15 hours.

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