A method for synthesizing chiral diols

Abstract

This invention discloses a method for synthesizing chiral diols, belonging to the field of organic synthesis technology. The chiral diol is a chiral 1,2-diol or 1,3-diol. This invention uses a brominated derivative (aryl brominated or alkenyl brominated) and a diol precursor as substrates. Under ultraviolet light irradiation in the presence of a ligand, a photocatalyst, and a nickel catalyst, a protected chiral diol is obtained, followed by deprotection to yield the chiral diol; alternatively, a one-pot synthesis of chiral diols can be performed starting from ethylene glycol or 1,3-propanediol. This invention utilizes a photo / nickel synergistic catalytic strategy to achieve the synthesis of 1,2-diols or 1,3-diols at the ortho-oxygen C(sp) position. 3 This invention enables stereoselective arylation or alkenylation of the 1,2-H bond under mild conditions and with broad substrate adaptability. The chiral 1,2-diols or 1,3-diols prepared by the method of this invention can be used to synthesize a variety of natural products, commercially available drugs, and chiral ligands through subsequent transformations, demonstrating significant synthetic value.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis technology, and specifically to a method for synthesizing chiral diols. Background Technology

[0002] Chiral diols are widely found in drug molecules and natural products, representing an important class of molecular structures. Statistics show that in 2022, 20% of the top 200 best-selling small molecule drugs contained chiral diol structural units. Among them, chiral 1,2-diols and 1,3-diols are also important intermediates in the synthesis of various chiral catalysts, drugs, natural products, and fine chemicals, and have wide applications in organic synthesis.

[0003] However, the synthesis of chiral 1,2-diols or 1,3-diols in the past relied on asymmetric bihydroxylation of alkenes, asymmetric reduction of carbonyl compounds, or asymmetric resolution, which had drawbacks such as high reaction costs, difficulty in preparing raw materials, low substrate universality, and poor atom economy. Summary of the Invention

[0004] To address the shortcomings of the existing technologies, this invention provides a method for synthesizing chiral diols. By utilizing photo-induced hydrogen atom transfer and nickel-co-catalyzed strategies, the carbon-hydrogen bonds of the diol precursor are directly broken to achieve enantioselective arylation and alkenylation, thus preparing a series of chiral diols. The synthesized chiral diols can be used to synthesize various commercially available drugs through subsequent transformations, demonstrating significant synthetic value.

[0005] To achieve the above objectives, the specific technical solution of the present invention is as follows:

[0006] A method for synthesizing a chiral diol, wherein the chiral diol is a chiral 1,2-diol or a chiral 1,3-diol; the chiral diol is synthesized using one of the following two methods;

[0007] Method I includes the following steps: under an inert atmosphere, the ligand, nickel catalyst and organic solvent are mixed for 1-2 h, a photocatalyst, a base, a bromide, and a diol precursor are added, and the mixture is reacted at 25 °C for 48-80 h under ultraviolet light irradiation to obtain a protected chiral diol. The protected chiral diol is then deprotected to obtain a chiral diol.

[0008] Method II includes the following steps: under an inert atmosphere, ethylene glycol or 1,3-propanediol is first subjected to a protective reaction, and then a ligand, nickel catalyst, photocatalyst, base, bromide, and organic solvent are added. The reaction is continued at 25 °C under ultraviolet light irradiation for 48-80 h to obtain a chiral diol.

[0009] The brominated product is an aryl bromide or an alkenyl bromide.

[0010] Preferably, the ligand is selected from one of the following structures:

[0011]

[0012] Preferably, the ligand is (4R,4'R)-2,2'-(propane-2,2-diyl)bis(5,5-dimethyl-4-phenyl-4,5-dihydrooxazole) (i.e., the structure shown in E).

[0013] Preferably, the photocatalyst is selected from one of the following structures:

[0014]

[0015] More preferably, the photocatalyst is tetrabutylammonium decatungstate (TBADT, i.e., the structure shown in F).

[0016] Preferably, the nickel catalyst includes, but is not limited to, one of nickel chloride, nickel bromide, nickel chloride ethylene glycol dimethyl ether, nickel bromide ethylene glycol dimethyl ether, cyclooctadiene nickel, nickel acetylacetone, nickel perchlorate, nickel iodide, or nickel acetate tetrahydrate.

[0017] More preferably, the nickel catalyst is nickel bromide ethylene glycol dimethyl ether.

[0018] Preferably, the brominated product is selected from one of the following structures:

[0019]

[0020] Preferably, the diol precursor is selected from one of the following structures:

[0021]

[0022] More preferably, the diol precursor is 2,2-dimethyl-1,3-dioxane (i.e., the structure shown in 1b) or 2,2-dimethyl-1,3-dioxane (i.e., the structure shown in 2b).

[0023] Preferably, the alkali includes, but is not limited to, one of sodium carbonate, potassium carbonate, potassium phosphate, sodium bicarbonate, cesium carbonate, sodium phosphate, sodium acetate, pyridine, 1,4-diazabicyclo[2.2.2]octane, and 2,6-dimethylpyridine.

[0024] More preferably, the alkali is potassium phosphate.

[0025] Preferably, the organic solvent includes, but is not limited to, a mixture of one or more of ethyl acetate, trifluorotoluene, acetonitrile, or acetone.

[0026] Preferably, the molar ratio of the brominated product, diol precursor, nickel catalyst, ligand, photocatalyst, and base is 1: (5~10): 0.1: 0.15: 0.05: (1.2~1.5), wherein the concentration of the brominated product is 0.1~0.2 mol / L.

[0027] Preferably, the violet light is 390 nm violet light.

[0028] This invention uses brominated derivatives (aryl brominated or alkenyl brominated) and diol precursors as substrates. It utilizes a visible light-promoted hydrogen atom transfer (HAT) process to directly break the C-H bonds of the diol precursors, generating an oxygen ortho-radical. Then, under the synergistic catalysis of a chiral nickel catalyst, and with the addition of specific ligands, it couples with the brominated derivatives (aryl brominated or alkenyl brominated) to obtain a protected chiral diol with high optical purity. The protected chiral diol is then deprotected to yield the chiral diol. This invention employs a photo / nickel synergistic catalysis strategy to achieve stereoselective arylation and alkenylation of the oxygen ortho-C-H bonds in the diol precursor. The chiral diols prepared by this method can be used for the synthesis of various natural products, commercially available drugs, and chiral ligands through subsequent transformations, demonstrating significant synthetic value.

[0029] Compared with the prior art, the advantages of the present invention are:

[0030] 1. This invention provides a strategy of photocatalyzed hydrogen atom transfer and nickel synergistic catalysis. Method I directly breaks the C-H bonds of diol precursors to achieve enantioselective arylation and alkenylation, preparing a series of chiral diols. Method II starts from inexpensive and readily available ethylene glycol or 1,3-propanediol and synthesizes chiral diols with high optical purity in a one-pot process. Both methods simplify the synthesis steps of chiral diols, avoid the use of precious metal catalysts and equivalent redox reagents, and greatly reduce the synthesis cost.

[0031] 2. The method of this invention has mild reaction conditions, good functional group tolerance, and a wide range of applicable substrates. It is an efficient, green, and inexpensive method for synthesizing chiral diols. Detailed Implementation

[0032] The technical solution of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0033] This invention provides a method for synthesizing a chiral diol, wherein the chiral diol is a chiral 1,2-diol or a chiral 1,3-diol; the chiral diol is synthesized using one of the following two methods;

[0034] Method I includes the following steps: under an inert atmosphere, the ligand, nickel catalyst and organic solvent are mixed for 1-2 h, a photocatalyst, a base, a bromide, and a diol precursor are added, and the mixture is reacted at 25 °C for 48-80 h under ultraviolet light irradiation to obtain a protected chiral diol. The protected chiral diol is then deprotected to obtain a chiral diol.

[0035] Method II includes the following steps: under an inert atmosphere, ethylene glycol or 1,3-propanediol is first subjected to a protective reaction, and then a ligand, nickel catalyst, photocatalyst, base, bromide, and organic solvent are added. The reaction is continued at 25 °C under ultraviolet light irradiation for 48-80 h to obtain a chiral diol.

[0036] The brominated product is an aryl bromide or an alkenyl bromide.

[0037] In some examples, the ligand is selected from one of the following structures:

[0038]

[0039] In some examples, the photocatalyst is selected from one of the following structures:

[0040]

[0041] In some examples, the nickel catalyst includes, but is not limited to, one of nickel chloride, nickel bromide, nickel chloride ethylene glycol dimethyl ether, nickel bromide ethylene glycol dimethyl ether, cyclooctadiene nickel, nickel acetylacetone, nickel perchlorate, nickel iodide, or nickel acetate tetrahydrate.

[0042] In some examples, the brominated product is selected from one of the following structures:

[0043]

[0044] In some examples, the diol precursor is selected from one of the following structures:

[0045]

[0046] The diol precursor can be prepared using existing technology or purchased directly.

[0047] In some examples, the base includes, but is not limited to, one of sodium carbonate, potassium carbonate, potassium phosphate, sodium bicarbonate, cesium carbonate, sodium phosphate, sodium acetate, pyridine, 1,4-diazabicyclo[2.2.2]octane, and 2,6-dimethylpyridine.

[0048] In some examples, the organic solvent includes, but is not limited to, a mixture of one or more of ethyl acetate, trifluorotoluene, acetonitrile, or acetone.

[0049] In some examples, the molar ratio of the brominated product, diol precursor, nickel catalyst, ligand, photocatalyst, and base is 1: (5~10): 0.1: 0.15: 0.05: (1.2~1.5), wherein the concentration of the brominated product is 0.1~0.2 mol / L.

[0050] In the following specific embodiments, the protected chiral diol is deprotected to obtain a chiral diol, which is achieved using existing technology, such as acid hydrolysis; the protection reaction of the ethylene glycol or 1,3-propanediol is achieved using existing technology, such as reacting with acetone under acidic conditions to obtain protected ethylene glycol or 1,3-propanediol; all raw materials and reagents used are commercially available.

[0051] Example 1

[0052]

[0053] Preparation of protected chiral 1,2-diol 1c: Under an argon atmosphere, E (0.03 mmol), nickel bromide ethylene glycol dimethyl ether (0.02 mmol), and acetone (0.5 mL) were added to a reaction tube equipped with a magnetic dome. After stirring at room temperature for 1 h, TBADT (0.01 mmol), potassium phosphate (0.24 mmol), 1a (0.2 mmol), 1b (1.0 mmol), and trifluorotoluene (0.5 mL) were added. The reaction was carried out under ultraviolet light (10 W, 390 nm) at 25 °C for 60 h. Product 1c (34.8 mg, 71% yield, 90% ee) was obtained by column chromatography.

[0054] 1 H NMR (600 MHz, CDCl3) δ 8.07 – 7.89 (m, 2H), 7.63 – 7.36 (m, 2H), 5.14 (t, J = 7.1 Hz, 1H), 4.35 (dd, J = 8.2, 6.4 Hz, 1H), 3.69 (t, J = 8.0Hz, 1H), 2.60 (s, 3H), 1.56 (s, 3H), 1.50 (s, 3H). 13 C NMR (151 MHz, CDCl3) δ197.7, 144.8, 136.8, 128.6, 126.2, 110.2, 77.4, 71.4, 26.6, 26.5, 25.9. HRMS: (APCI) calcd for C 13 H 17 O3 + [M+H] +221.1172, found 221.1168.

[0055] Example 2

[0056]

[0057] Preparation of protected chiral 1,2-diol 2c: Under an argon atmosphere, E (0.03 mmol), nickel bromide ethylene glycol dimethyl ether (0.02 mmol), and acetone (0.5 mL) were added to a reaction tube equipped with a magnetic dome. After stirring at room temperature for 1 h, TBADT (0.01 mmol), potassium phosphate (0.24 mmol), 2a (0.2 mmol), 1b (1.0 mmol), and trifluorotoluene (0.5 mL) were added. The reaction was carried out under ultraviolet light (10 W, 390 nm) at 25 °C for 60 h. Product 2c (25.2 mg, 62% yield, 93% ee) was obtained by column chromatography.

[0058] 1 H NMR (400 MHz, CDCl3) δ 7.68 – 7.60 (m, 2H), 7.51 – 7.43 (m, 2H), 5.11 (t, J = 7.0 Hz, 1H), 4.35 (dd, J = 8.3, 6.4 Hz, 1H), 3.66 (t, J = 7.9Hz, 1H), 1.54 (s, 3H), 1.48 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 145.1, 132.5,126.8, 118.8, 111.9, 110.5, 71.4, 26.5, 25.8. HRMS: (APCI) calcd for C 12 H 14 NO2 + [M+H] + 204.1019 was found as 204.1014.

[0059] Example 3

[0060]

[0061] Preparation of protected chiral 1,2-diol 3c: Under an argon atmosphere, E (0.03 mmol), nickel bromide ethylene glycol dimethyl ether (0.02 mmol), and acetone (0.5 mL) were added to a reaction tube equipped with a magnetic dome. After stirring at room temperature for 1 h, TBADT (0.01 mmol), potassium phosphate (0.24 mmol), 3a (0.2 mmol), 1b (1.0 mmol), and trifluorotoluene (0.5 mL) were added. The reaction was carried out under ultraviolet light (10 W, 390 nm) at 25 °C for 60 h. Product 3c (29.5 mg, 60% yield, 90% ee) was obtained by column chromatography.

[0062] 1 H NMR (600 MHz, CDCl3) δ 7.62 (d, J = 8.1 Hz, 2H), 7.48 (d, J = 8.0Hz, 2H), 5.13 (t, J = 7.0 Hz, 1H), 4.36 (dd, J = 8.3, 6.3 Hz, 1H), 3.69 (t, J= 8.0 Hz, 1H), 1.56 (s, 3H), 1.50 (s, 3H). 13 C NMR (151 MHz, CDCl3) δ 143.5,130.2 (q, J = 32.5 Hz), 126.3, 125.5 (q, J = 3.8 Hz), 124.1 (q, J = 272.0Hz), 110.2, 77.2, 71.5, 26.5, 25.8. 19 F NMR (565 MHz, CDCl3) δ -62.55.

[0063] Example 4

[0064]

[0065] Preparation of protected chiral 1,2-diol 4c: Under an argon atmosphere, E (0.03 mmol), nickel bromide ethylene glycol dimethyl ether (0.02 mmol), and acetone (0.5 mL) were added to a reaction tube equipped with a magnetic ball. After stirring at room temperature for 1 h, TBADT (0.01 mmol), potassium phosphate (0.24 mmol), 4a (45.8 mg, 0.2 mmol), 1b (1.0 mmol), and trifluorotoluene (0.5 mL) were added. The reaction was carried out under ultraviolet light (10 W, 390 nm) at 25 °C for 60 h. The product 4c (33.1 mg, 66% yield, 91% ee) was obtained by column chromatography.

[0066] 1 H NMR (600 MHz, CDCl3) δ 8.06 – 8.01 (m, 2H), 7.45 – 7.41 (m, 2H), 5.13 (dd, J = 7.8, 6.3 Hz, 1H), 4.39 (q, J = 7.1 Hz, 2H), 4.39 – 4.32 (m,1H), 3.69 (t, J = 8.0 Hz, 1H), 1.56 (s, 3H), 1.50 (s, 3H), 1.40 (t, J = 7.1Hz, 3H). 13 C NMR (151 MHz, CDCl3) δ 166.4, 144.4, 129.8, 125.9, 110.1, 77.4,71.5, 61.0, 26.5, 25.9, 14.3. HRMS: (APCI) calcd for C 14 H 19 O4 + [M+H] + 251.1278, found 251.1284.

[0067] Example 5

[0068]

[0069] Preparation of protected chiral 1,2-diol 5c: Under an argon atmosphere, E (0.03 mmol), nickel bromide ethylene glycol dimethyl ether (0.02 mmol), and acetone (0.5 mL) were added to a reaction tube equipped with a magnetic dome. After stirring at room temperature for 1 h, TBADT (0.01 mmol), potassium phosphate (0.24 mmol), 5a (35.0 mg, 0.2 mmol), 1b (1.0 mmol), and trifluorotoluene (0.5 mL) were added. The reaction was carried out under ultraviolet light (10 W, 390 nm) at 25 °C for 60 h. The product 5c (17.9 mg, 47% yield, 84% ee) was obtained by column chromatography.

[0070] 1H NMR (600 MHz, CDCl3) δ 7.38 – 7.31 (m, 2H), 7.08 – 6.99 (m, 2H), 5.05 (dd, J = 8.0, 6.2 Hz, 1H), 4.29 (dd, J = 8.2, 6.2 Hz, 1H), 3.67 (t, J =8.1 Hz, 1H), 1.55 (s, 3H), 1.48 (s, 3H). 13 C NMR (151 MHz, CDCl3) δ 162.6 (d, J= 246.2 Hz), 134.8 (d, J = 3.2 Hz), 128.0 (d, J = 8.2 Hz), 115.5 (d, J = 21.5Hz), 109.8, 77.4, 71.7, 26.6, 25.9. 19 F NMR (565 MHz, CDCl3) δ -114.3. HRMS: (ESI) calcd for C 11 H 13 FO2Na + [M+Na] + 219.0792, found 219.0790.

[0071] Example 6

[0072]

[0073] Preparation of protected chiral 1,2-diol 6c: Under an argon atmosphere, E (0.03 mmol), nickel bromide ethylene glycol dimethyl ether (0.02 mmol), and acetone (0.5 mL) were added to a reaction tube equipped with a magnetic stir bar. After stirring at room temperature for 1 h, TBADT (0.01 mmol), potassium phosphate (0.24 mmol), 6a (38.2 mg, 0.2 mmol), 1b (1.0 mmol), and trifluorotoluene (0.5 mL) were added. The reaction was carried out under ultraviolet light (10 W, 390 nm) at 25 °C for 60 h. The product 6c (27.5 mg, 65% yield, 91% ee) was obtained by column chromatography.

[0074] 1H NMR (600 MHz, CDCl3) δ 7.35 – 7.28 (m, 4H), 5.05 (dd, J = 7.9, 6.2Hz, 1H), 4.30 (dd, J = 8.2, 6.2 Hz, 1H), 3.66 (t, J = 8.1 Hz, 1H), 1.56 (s,3H), 1.48 (s,3H). 13 C NMR (151 MHz, CDCl3) δ 137.8, 133.8, 128.7, 127.5,109.9, 77.3, 71.6, 26.6, 25.9.

[0075] Example 7

[0076]

[0077] Preparation of protected chiral 1,2-diol 7c: Under an argon atmosphere, E (0.03 mmol), nickel bromide ethylene glycol dimethyl ether (0.02 mmol), and acetone (0.5 mL) were added to a reaction tube equipped with a magnetic dome. After stirring at room temperature for 1 h, TBADT (0.01 mmol), potassium phosphate (0.24 mmol), 7a (47.2 mg, 0.2 mmol), 1b (1.0 mmol), and trifluorotoluene (0.5 mL) were added. The reaction was carried out under ultraviolet light (10 W, 390 nm) at 25 °C for 60 h. The product 7c (33.3 mg, 65% yield, 93% ee) was obtained by column chromatography.

[0078] 1 H NMR (600 MHz, CDCl3) δ 7.97 – 7.92 (m, 2H), 7.59 – 7.55 (m, 2H), 5.16 (t, J = 7.0 Hz, 1H), 4.39 (dd, J = 8.3, 6.4 Hz, 1H), 3.70 (t, J = 7.9Hz, 1H), 3.05 (s, 3H), 1.56 (s, 3H), 1.50 (s, 3H). 13 C NMR (151 MHz, CDCl3) δ146.1, 140.1, 127.7, 126.9, 110.5, 77.0, 71.4, 44.6, 26.5, 25.8. HRMS: (APCI)calcd for C 12 H 17 O4S + [M+H]+ 257.0842, found 257.0849.

[0079] Example 8

[0080]

[0081] Preparation of protected chiral 1,2-diol 8c: Under an argon atmosphere, E (0.03 mmol), nickel bromide ethylene glycol dimethyl ether (0.02 mmol), and acetone (0.5 mL) were added to a reaction tube equipped with a magnetic dome. After stirring at room temperature for 1 h, TBADT (0.01 mmol), potassium phosphate (0.24 mmol), 8a (56.6 mg, 0.2 mmol), 1b (1.0 mmol), and trifluorotoluene (0.5 mL) were added. The reaction was carried out under ultraviolet light (10 W, 390 nm) at 25 °C for 60 h. The product 8c (34.0 mg, 58% yield, 88% ee) was obtained by column chromatography.

[0082] 1 H NMR (600 MHz, CDCl3) δ 7.83 – 7.77 (m, 2H), 7.39 – 7.34 (m, 2H), 5.09 (dd, J = 8.0, 6.3 Hz, 1H), 4.31 (dd, J = 8.2, 6.3 Hz, 1H), 3.68 (t, J =8.1 Hz, 1H), 1.55 (s, 3H), 1.49 (s, 3H), 1.34 (s, 12H). 13 C NMR (151 MHz, CDCl3) δ 142.3, 135.0, 125.4, 109.9, 83.8, 77.9, 71.6, 26.6, 26.0, 24.89,24.87.

[0083] Example 9

[0084]

[0085] Preparation of protected chiral 1,2-diol 9c: Under an argon atmosphere, E (0.03 mmol), nickel bromide ethylene glycol dimethyl ether (0.02 mmol), and acetone (0.5 mL) were added to a reaction tube equipped with a magnetic ball. After stirring at room temperature for 1 h, TBADT (0.01 mmol), potassium phosphate (0.24 mmol), 9a (48.2 mg, 0.2 mmol), 1b (1.0 mmol), and trifluorotoluene (0.5 mL) were added. The reaction was carried out under ultraviolet light (10 W, 390 nm) at 25 °C for 60 h. The product 9c (28.8 mg, 55% yield, 88% ee) was obtained by column chromatography.

[0086] 1 H NMR (600 MHz, CDCl3) δ 7.42 – 7.37 (m, 2H), 7.23 – 7.18 (m, 2H), 5.07 (dd, J = 7.8, 6.2 Hz, 1H), 4.31 (dd, J = 8.3, 6.3 Hz, 1H), 3.69 (t, J =8.1 Hz, 1H), 1.55 (s, 3H), 1.48 (s, 3H). 13 C NMR (151 MHz, CDCl3) δ 148.9 (q, J= 2.1 Hz), 138.0, 127.6, 121.1, 120.5 (q, J = 257.1 Hz), 110.0, 77.2, 71.6, 26.6, 25.8. 19 F NMR (565 MHz, CDCl3) δ -57.92. HRMS: (ESI) calcd for C 12 H 13 F3O3Na + [M+Na] + 285.0709, found 285.0703.

[0087] Example 10

[0088]

[0089] Preparation of protected chiral 1,2-diol 10c: Under an argon atmosphere, E (0.03 mmol), nickel bromide ethylene glycol dimethyl ether (0.02 mmol), and acetone (0.5 mL) were added to a reaction tube equipped with a magnetic dome. After stirring at room temperature for 1 h, TBADT (0.01 mmol), potassium phosphate (0.24 mmol), 10a (45.2 mg, 0.2 mmol), 1b (1.0 mmol), and trifluorotoluene (0.5 mL) were added. The reaction was carried out under ultraviolet light (10 W, 390 nm) at 25 °C for 60 h. The product 10c (28.2 mg, 57% yield, 88% ee) was obtained by column chromatography.

[0090] 1 H NMR (600 MHz, CDCl3) δ 7.35 – 7.28 (m, 2H), 6.92 – 6.87 (m, 2H), 5.02 (dd, J = 8.1, 6.1 Hz, 1H), 4.26 (dd, J = 8.2, 6.1 Hz, 1H), 4.19 (t, J =6.4 Hz, 2H), 3.68 (t, J = 8.2 Hz, 1H), 2.82 (t, J = 6.4 Hz, 2H), 1.54 (s,3H), 1.47 (s, 3H). 13 C NMR (151 MHz, CDCl3) δ 157.6, 132.3, 127.8, 117.1,114.8, 109.6, 77.6, 71.7, 62.7, 26.7, 26.0, 18.6. HRMS: (ESI) calcd forC 14 H 17 O3Na + [M+Na] + 270.1101, found 270.1102.

[0091] Example 11

[0092]

[0093] Preparation of protected chiral 1,2-diol 11c: Under an argon atmosphere, E (0.03 mmol), nickel bromide ethylene glycol dimethyl ether (0.02 mmol), and acetone (0.5 mL) were added to a reaction tube equipped with a magnetic dome. After stirring at room temperature for 1 h, TBADT (0.01 mmol), potassium phosphate (0.24 mmol), 11a (46.6 mg, 0.2 mmol), 1b (102.1 mg, 1.0 mmol), and trifluorotoluene (0.5 mL) were added. The reaction was carried out under ultraviolet light (10 W, 390 nm) at 25 °C for 60 h. The product 11c (25.9 mg, 51% yield, 87% ee) was obtained by column chromatography.

[0094] 1 H NMR (400 MHz, CDCl3) δ 7.65 – 7.54 (m, 4H), 7.44 (dd, J = 7.9, 5.8Hz, 4H), 7.39 – 7.32 (m, 1H), 5.13 (dd, J = 8.1, 6.2 Hz, 1H), 4.34 (dd, J =8.2, 6.2 Hz, 1H), 3.77 (t, J = 8.1 Hz, 1H), 1.58 (s, 3H), 1.51 (s, 3H). 13 C NMR(101 MHz, CDCl3) δ 141.0, 140.8, 138.0, 128.8, 127.34, 127.30, 127.1, 126.7,109.8, 77.7, 71.6, 26.6, 26.0. HRMS: (ESI) calcd for C 17 H 18 O2Na + [M+Na] + 277.1199, found 277.1201.

[0095] Example 12

[0096]

[0097] Preparation of protected chiral 1,2-diol 12c: Under an argon atmosphere, E (0.03 mmol), nickel bromide ethylene glycol dimethyl ether (0.02 mmol), and acetone (0.5 mL) were added to a reaction tube equipped with a magnetic dome. After stirring at room temperature for 1 h, TBADT (0.01 mmol), potassium phosphate (0.24 mmol), 12a (0.2 mmol), 1b (1.0 mmol), and trifluorotoluene (0.5 mL) were added. The reaction was carried out under ultraviolet light (10 W, 390 nm) at 25 °C for 60 h. After concentration, rapid column chromatography was performed to obtain product 12c (27.1 mg, 64% yield, 89% ee).

[0098] 1 H NMR (600 MHz, CDCl3) δ 7.37 (d, J = 2.1 Hz, 1H), 7.30 – 7.25 (m,2H), 7.25 – 7.21 (m, 1H), 5.04 (dd, J = 7.8, 6.3 Hz, 1H), 4.31 (dd, J = 8.3,6.3 Hz, 1H), 3.68 (t, J = 8.0 Hz, 1H), 1.55 (s, 3H), 1.48 (s, 3H). 13 C NMR (151MHz, CDCl3) δ 141.4, 134.5, 129.8, 128.2, 126.3, 124.3, 110.1, 77.2, 71.5,26.5, 25.9.

[0099] Example 13

[0100]

[0101] Preparation of protected chiral 1,2-diol 13c: Under an argon atmosphere, E (0.03 mmol), nickel bromide ethylene glycol dimethyl ether (0.02 mmol), and acetone (0.5 mL) were added to a reaction tube equipped with a magnetic ball. After stirring at room temperature for 1 h, TBADT (0.01 mmol), potassium phosphate (0.24 mmol), 13a (43.0 mg, 0.2 mmol), 1b (1.0 mmol), and trifluorotoluene (0.5 mL) were added. The reaction was carried out under ultraviolet light (10 W, 390 nm) at 25 °C for 60 h. The product 13c (24.5 mg, 52% yield, 85% ee) was obtained by column chromatography.

[0102] 1H NMR (600 MHz, CDCl3) δ 7.36 (t, J = 7.9 Hz, 1H), 7.22 (ddt, J =7.7, 1.6, 0.8 Hz, 1H), 7.11 (t, J = 2.0 Hz, 1H), 7.03 (ddd, J = 8.1, 2.4, 1.0Hz, 1H), 5.07 (dd, J = 7.9, 6.2 Hz, 1H), 4.31 (dd, J = 8.2, 6.2 Hz, 1H), 3.71(t, J = 8.1 Hz, 1H), 2.30 (s, 3H), 1.54 (s, 3H), 1.48 (s, 3H). 13 C NMR (151MHz, CDCl3) δ 169.4, 150.9, 141.1, 129.6, 123.5, 121.2, 119.3, 109.9, 77.3,71.5, 26.5, 25.9, 21.1. HRMS: (ESI) calcd for C 13 H 17 O4 + [M+H] + 237.1121, found 237.1126.

[0103] Example 14

[0104]

[0105] Preparation of protected chiral 1,2-diol 14c: Under an argon atmosphere, E (0.03 mmol), nickel bromide ethylene glycol dimethyl ether (0.02 mmol), and acetone (0.5 mL) were added to a reaction tube equipped with a magnetic dome. After stirring at room temperature for 1 h, TBADT (0.01 mmol), potassium phosphate (0.24 mmol), 14a (0.2 mmol), 1b (1.0 mmol), and trifluorotoluene (0.5 mL) were added. The reaction was carried out under ultraviolet light (10 W, 390 nm) at 25 °C for 60 h. The product 14c (25.9 mg, 61% yield, 85% ee) was obtained by column chromatography.

[0106] 1H NMR (600 MHz, CDCl3) δ 7.63 (dd, J = 7.9, 1.7 Hz, 1H), 7.33 (dd, J= 7.9, 1.3 Hz, 1H), 7.29 (td, J = 7.5, 1.3 Hz, 1H), 7.22 (td, J = 7.6, 1.8Hz, 1H), 5.42 (t, J = 6.9 Hz, 1H), 4.54 (dd, J = 8.3, 6.6 Hz, 1H), 3.64 (dd,J = 8.3, 7.3 Hz, 1H), 1.57 (s, 3H), 1.51 (s, 3H). 13 C NMR (151 MHz, CDCl3) δ138.0, 131.7, 129.2, 128.7, 127.0, 126.7, 109.7, 74.9, 70.4, 26.4, 25.7.

[0107] Example 15

[0108]

[0109] Preparation of protected chiral 1,2-diol 15c: Under an argon atmosphere, E (0.03 mmol), nickel bromide ethylene glycol dimethyl ether (0.02 mmol), and acetone (0.5 mL) were added to a reaction tube equipped with a magnetic dome. After stirring at room temperature for 1 h, TBADT (0.01 mmol), potassium phosphate (0.24 mmol), 15a (0.2 mmol), 1b (1.0 mmol), and trifluorotoluene (0.5 mL) were added. The reaction was carried out under ultraviolet light (10 W, 390 nm) at 25 °C for 60 h. The product 15c (41.4 mg, 66% yield, 91% ee) was obtained by column chromatography.

[0110] 1 H NMR (600 MHz, CDCl3) δ 7.86 – 7.76 (m, 3H), 5.18 (t, J = 6.9 Hz, 1H), 4.41 (dd, J = 8.4, 6.4 Hz, 1H), 3.72 (dd, J = 8.3, 7.4 Hz, 1H), 1.57 (s,3H), 1.50 (s,3H). 13C NMR (151 MHz, CDCl3) δ 142.5, 131.9 (q, J = 33.3 Hz), 126.2 (q, J = 3.9 Hz), 123.2 (q, J = 272.7 Hz), 121.9 (p, J = 3.9 Hz), 110.7,76.5, 71.3, 26.4, 25.7. 19 F NMR (565 MHz, CDCl3) δ -62.93. HRMS: (APCI) calcdfor C 13 H 13 F6O2 + [M+H] + 315.0814, found 315.0811.

[0111] Example 16

[0112]

[0113] Preparation of protected chiral 1,2-diol 16c: Under an argon atmosphere, E (0.03 mmol), nickel bromide ethylene glycol dimethyl ether (0.02 mmol), and acetone (0.5 mL) were added to a reaction tube equipped with a magnetic dome. After stirring at room temperature for 1 h, TBADT (0.01 mmol), potassium phosphate (0.24 mmol), 16a (0.2 mmol), 1b (1.0 mmol), and trifluorotoluene (0.5 mL) were added. The reaction was carried out under ultraviolet light (10 W, 390 nm) at 25 °C for 60 h. The product 16c (28.2 mg, 48% yield, 91% ee) was obtained by column chromatography.

[0114] 1 H NMR (600 MHz, CDCl3) δ 7.23 (ddd, J = 8.3, 2.1, 0.6 Hz, 1H), 7.21 (d, J = 2.0 Hz, 1H), 7.17 (d, J = 8.3 Hz, 1H), 5.05 (dd, J = 7.8, 6.2 Hz,1H), 4.30 (dd, J = 8.3, 6.2 Hz, 1H), 3.71 (t, J = 8.0 Hz, 1H), 2.29 (s, 3H), 2.28 (s, 3H), 1.53 (s, 3H), 1.47 (s, 3H). 13C NMR (151 MHz, CDCl3) δ 168.3,168.2, 142.1, 141.6, 138.3, 124.2, 123.5, 121.2, 110.0, 77.0, 71.4, 26.6,25.9, 20.67, 20.66. HRMS: (ESI) calcd for C 15 H 18 O6Na + [M+Na] + 317.0996, found 317.0988.

[0115] Example 17

[0116]

[0117] Preparation of protected chiral 1,2-diol 17c: Under an argon atmosphere, E (0.03 mmol), nickel bromide ethylene glycol dimethyl ether (0.02 mmol), and acetone (0.5 mL) were added to a reaction tube equipped with a magnetic stir bar. After stirring at room temperature for 1 h, TBADT (0.01 mmol), potassium phosphate (0.24 mmol), 17a (0.2 mmol), 1b (1.0 mmol), and trifluorotoluene (0.5 mL) were added. The reaction was carried out under ultraviolet light (10 W, 390 nm) at 25 °C for 60 h. The product 17c (25.3 mg, 54% yield, 93% ee) was obtained by column chromatography.

[0118] 1 H NMR (600 MHz, CDCl3) δ 7.91 (d, J = 7.9 Hz, 1H), 7.56 – 7.53 (m,1H), 7.50 (dd, J = 7.8, 1.3 Hz, 1H), 5.33 (d, J = 2.0 Hz, 2H), 5.23 – 5.18(m, 1H), 4.40 (dd, J = 8.3, 6.4 Hz, 1H), 3.70 (dd, J = 8.3, 7.6 Hz, 1H), 1.58(s, 3H), 1.51 (s, 3H). 13 C NMR (151 MHz, CDCl3) δ 170.8, 147.2, 146.6, 127.0,126.0, 125.5, 119.4, 110.4, 77.3, 71.5, 69.6, 26.5, 25.8. HRMS: (ESI) calcdfor C 13 H15 O4 + [M+H] + 235.0965, found 235.0966.

[0119] Example 18

[0120]

[0121] Preparation of protected chiral 1,2-diol 18c: Under an argon atmosphere, E (0.03 mmol), nickel bromide ethylene glycol dimethyl ether (0.02 mmol), and acetone (0.5 mL) were added to a reaction tube equipped with a magnetic dome. After stirring at room temperature for 1 h, TBADT (0.01 mmol), potassium phosphate (0.24 mmol), 18a (0.2 mmol), 1b (1.0 mmol), and trifluorotoluene (0.5 mL) were added. The reaction was carried out under ultraviolet light (10 W, 390 nm) at 25 °C for 60 h. The product 18c (20.5 mg, 45% yield, 86% ee) was obtained by column chromatography.

[0122] 1 H NMR (600 MHz, CDCl3) δ 7.88 – 7.82 (m, 4H), 7.52 – 7.46 (m, 3H), 5.26 (dd, J = 8.0, 6.3 Hz, 1H), 4.39 (dd, J = 8.2, 6.3 Hz, 1H), 3.81 (t, J =8.1 Hz, 1H), 1.63 (s, 3H), 1.55 (s, 3H). 13 C NMR (151 MHz, CDCl3) δ 136.5,133.24, 133.23, 128.5, 128.0, 127.8, 126.3, 126.1, 125.3, 123.9, 109.9, 78.1,71.6, 26.7, 26.0.

[0123] Example 19

[0124]

[0125] Preparation of protected chiral 1,2-diol 19c: Under an argon atmosphere, E (0.03 mmol), nickel bromide ethylene glycol dimethyl ether (0.02 mmol), and acetone (0.5 mL) were added to a reaction tube equipped with a magnetic stir bar. After stirring at room temperature for 1 h, TBADT (0.01 mmol), potassium phosphate (0.24 mmol), 19a (0.2 mmol), 1b (1.0 mmol), and trifluorotoluene (0.5 mL) were added. The reaction was carried out under ultraviolet light (10 W, 390 nm) at 25 °C for 60 h. The product 19c (27.3 mg, 51% yield, 88% ee) was obtained by column chromatography.

[0126] 1 H NMR (600 MHz, CDCl3) δ 8.00 – 7.93 (m, 2H), 7.60 – 7.53 (m, 2H), 7.48 – 7.44 (m, 2H), 7.37 – 7.33 (m, 1H), 5.25 (dd, J = 8.1, 6.2 Hz, 1H), 4.38 (dd, J = 8.3, 6.2 Hz, 1H), 3.80 (t, J = 8.2 Hz, 1H), 1.63 (s, 3H), 1.54(s, 3H). 13 C NMR (151 MHz, CDCl3) δ 156.6, 156.0, 133.6, 127.3, 125.5, 124.5,124.0, 122.8, 120.7, 118.5, 111.8, 111.7, 109.8, 78.1, 72.0, 26.8, 26.0.HRMS: (ESI) calcd for C 17 H 16 O3Na + [M+Na] + 291.0992, found 291.0988.

[0127] Example 20

[0128]

[0129] Preparation of protected chiral 1,2-diol 20c: Under an argon atmosphere, E (0.03 mmol), nickel bromide ethylene glycol dimethyl ether (0.02 mmol), and acetone (0.5 mL) were added to a reaction tube equipped with a magnetic dome. After stirring at room temperature for 1 h, TBADT (0.01 mmol), potassium phosphate (0.24 mmol), 20a (0.2 mmol), 1b (1.0 mmol), and trifluorotoluene (0.5 mL) were added. The reaction was carried out under ultraviolet light (10 W, 390 nm) at 25 °C for 60 h. The product 20c (31.8 mg, 56% yield, 90% ee) was obtained by column chromatography.

[0130] 1 H NMR (600 MHz, CDCl3) δ 8.21 – 8.15 (m, 2H), 7.89 – 7.82 (m, 2H), 7.49 – 7.44 (m, 3H), 5.27 (dd, J = 8.0, 6.2 Hz, 1H), 4.40 (dd, J = 8.3, 6.3Hz, 1H), 3.81 (t, J = 8.2 Hz, 1H), 1.64 (s, 3H), 1.56 (s, 3H). 13 C NMR (151MHz, CDCl3) δ 139.9, 139.2, 135.7, 135.6, 135.3, 126.9, 124.9, 124.4, 123.0,122.9, 121.7, 119.3, 109.9, 78.1, 71.9, 26.7, 26.0. HRMS: (ESI) calcd forC 17 H 16 O2SNa + [M+Na] + 307.0763, found 307.0763.

[0131] Example 21

[0132]

[0133] Preparation of protected chiral 1,2-diol 21c: Under an argon atmosphere, E (0.03 mmol), nickel bromide ethylene glycol dimethyl ether (0.02 mmol), and acetone (0.5 mL) were added to a reaction tube equipped with a magnetic dome. After stirring at room temperature for 1 h, TBADT (0.01 mmol), potassium phosphate (0.24 mmol), 21a (0.2 mmol), 1b (1.0 mmol), and trifluorotoluene (0.5 mL) were added. The reaction was carried out under ultraviolet light (10 W, 390 nm) at 25 °C for 60 h. The product 21c (24.8 mg, 53% yield, 89% ee) was obtained by column chromatography.

[0134] 1 H NMR (600 MHz, CDCl3) δ 7.87 (d, J = 8.3 Hz, 1H), 7.83 (d, J = 1.6Hz, 1H), 7.46 (d, J = 5.4 Hz, 1H), 7.37 – 7.31 (m, 2H), 5.21 (dd, J = 8.0, 6.2 Hz, 1H), 4.35 (dd, J = 8.2, 6.2 Hz, 1H), 3.76 (t, J = 8.1 Hz, 1H), 1.59 (s, 3H), 1.57 (s, 3H). 13 C NMR (151 MHz, CDCl3) δ 139.8, 139.4, 135.3, 127.1,123.8, 122.7, 122.5, 121.3, 109.8, 78.1, 71.9, 26.7, 26.0. HRMS: (ESI) calcdfor C 13 H 14 O2SNa + [M+Na] + 257.0607, found 257.0609.

[0135] Example 22

[0136]

[0137] Preparation of protected chiral 1,2-diol 22c: Under an argon atmosphere, E (0.03 mmol), nickel bromide ethylene glycol dimethyl ether (0.02 mmol), and acetone (0.5 mL) were added to a reaction tube equipped with a magnetic dome. After stirring at room temperature for 1 h, TBADT (0.01 mmol), potassium phosphate (0.24 mmol), 22a (0.2 mmol), 1b (1.0 mmol), and trifluorotoluene (0.5 mL) were added. The reaction was carried out under ultraviolet light (10 W, 390 nm) at 25 °C for 60 h. The product 22c (30.1 mg, 61% yield, 91% ee) was obtained by column chromatography.

[0138] 1 H NMR (600 MHz, CDCl3) δ 8.71 (d, J = 2.1 Hz, 1H), 7.90 (dd, J = 8.2,2.1 Hz, 1H), 7.69 (d, J = 8.1 Hz, 1H), 5.19 (t, J = 6.8 Hz, 1H), 4.42 (dd, J= 8.4, 6.5 Hz, 1H), 3.77 – 3.71 (m, 1H), 1.56 (s, 3H), 1.50 (s, 3H). 13 C NMR(151 MHz, CDCl3) δ 148.1, 147.9 (q, J = 34.7 Hz), 138.7, 135.0, 121.5 (q, J =274.8 Hz), 120.4 (q, J = 3.0 Hz), 110.7, 75.0, 71.2, 26.4, 25.6. 19 F NMR (565MHz, CDCl3) δ -67.88. HRMS: (APCI) calcd for C 11 H 13 F3NO2 + [M+H] + 248.0893, found 248.0887.

[0139] Example 23

[0140]

[0141] Preparation of protected chiral 1,2-diol 23c: Under an argon atmosphere, E (0.03 mmol), nickel bromide ethylene glycol dimethyl ether (0.02 mmol), and acetone (0.5 mL) were added to a reaction tube equipped with a magnetic dome. After stirring at room temperature for 1 h, TBADT (0.01 mmol), potassium phosphate (0.24 mmol), 23a (0.2 mmol), 1b (1.0 mmol), and trifluorotoluene (0.5 mL) were added. The reaction was carried out under ultraviolet light (10 W, 390 nm) at 25 °C for 60 h. The product 23c (30.6 mg, 75% yield, 90% ee) was obtained by column chromatography.

[0142] 1 H NMR (600 MHz, CDCl3) δ 8.68 (d, J = 2.2 Hz, 1H), 7.85 (dd, J = 8.0,2.2 Hz, 1H), 7.70 (d, J = 7.9 Hz, 1H), 5.16 (t, J = 6.8 Hz, 1H), 4.40 (dd, J= 8.4, 6.5 Hz, 1H), 3.71 (dd, J = 8.5, 7.1 Hz, 1H), 1.54 (s, 3H), 1.48 (s,3H). 13 C NMR (151 MHz, CDCl3) δ 149.2, 139.5, 134.6, 133.3, 128.3, 117.1,110.8, 75.0, 71.0, 26.4, 25.6. HRMS: (APCI) calcd for C 11 H 13 N2O2 + [M+H] + 205.0972, found 205.0967.

[0143] Example 24

[0144]

[0145] Preparation of protected chiral 1,2-diol 24c: Under an argon atmosphere, E (0.03 mmol), nickel bromide ethylene glycol dimethyl ether (0.02 mmol), and acetone (0.5 mL) were added to a reaction tube equipped with a magnetic dome. After stirring at room temperature for 1 h, TBADT (0.01 mmol), potassium phosphate (0.24 mmol), 24a (0.2 mmol), 1b (1.0 mmol), and trifluorotoluene (0.5 mL) were added. The reaction was carried out under ultraviolet light (10 W, 390 nm) at 25 °C for 60 h. The product 24c (55.2 mg, 72% yield, dr > 19 / 1) was obtained by column chromatography.

[0146] 1 H NMR (600 MHz, CDCl3) δ 7.74 – 7.68 (m, 2H), 7.42 – 7.38 (m, 2H), 7.30 – 7.26 (m, 2H), 7.26 – 7.22 (m, 1H), 7.14 – 7.10 (m, 2H), 6.62 (d, J =7.5 Hz, 1H), 5.12 – 5.05 (m, 2H), 4.32 (dd, J = 8.2, 6.3 Hz, 1H), 3.76 (s,3H), 3.67 (t, J = 8.0 Hz, 1H), 3.28 (dd, J = 13.9, 5.8 Hz, 1H), 3.21 (dd, J =13.9, 5.5 Hz, 1H), 1.54 (s, 3H), 1.48 (s, 3H). 13 C NMR (151 MHz, CDCl3) δ172.1, 166.5, 143.4, 135.8, 133.5, 129.3, 128.7, 127.3, 127.2, 126.3, 110.1,77.3, 71.5, 53.5, 52.5, 37.9, 26.5, 25.9. HRMS: (APCI) calcd for C 22 H 26 NO5 + [M+H] + 384.1804, found 384.1800.

[0147] Example 25

[0148]

[0149] Preparation of protected chiral 1,2-diol 25c: Under an argon atmosphere, E (0.03 mmol), nickel bromide ethylene glycol dimethyl ether (0.02 mmol), and acetone (0.5 mL) were added to a reaction tube equipped with a magnetic dome. After stirring at room temperature for 1 h, TBADT (0.01 mmol), potassium phosphate (0.24 mmol), 25a (0.2 mmol), 1b (1.0 mmol), and trifluorotoluene (0.5 mL) were added. The reaction was carried out under ultraviolet light (10 W, 390 nm) at 25 °C for 60 h. The product 25c (55.0 mg, 54% yield, dr > 19 / 1) was obtained by column chromatography.

[0150] 1 H NMR (600 MHz, CDCl3) δ 7.54 – 7.46 (m, 2H), 7.47 – 7.39 (m, 2H), 7.36 – 7.27 (m, 3H), 7.25 – 7.05 (m, 2H), 7.01 – 6.94 (m, 1H), 6.89 – 6.74(m, 1H), 6.08 – 5.10 (m, 1H), 5.09 – 4.91 (m, 1H), 4.37 – 4.28 (m, 1H), 4.26– 4.09 (m, 1H), 3.73 – 3.64 (m, 1H), 2.92 – 2.64 (m, 3H), 2.41 – 1.77 (m,4H), 1.58 – 1.45 (m, 6H). 13C NMR (151 MHz, CDCl3) δ 172.5, 172.2, 147.0,146.7, 141.98, 140.8, 138.4, 137.9, 136.3, 135.7, 135.6, 132.5, 132.3, 131.1,131.0, 130.7, 130.6, 130.3, 130.2, 130.1, 128.12, 128.07, 127.94, 127.93,127.8, 127.6, 127.5, 127.3, 127.27, 127.25, 126.7, 126.51, 126.49, 126.3,110.03, 110.00, 77.5, 71.61, 71.56, 58.6, 52.8, 43.1, 42.7, 33.1, 30.1, 20.0,28.9, 26.6, 25.92, 25.86, 22.6, 21.2. HRMS: (ESI) calcd for C 29 H 30 Cl2NO3 + [M+H] + 510.1597, found 510.1591.

[0151] Example 26

[0152]

[0153] Preparation of protected chiral 1,2-diol 26c: Under an argon atmosphere, E (0.03 mmol), nickel bromide ethylene glycol dimethyl ether (0.02 mmol), and acetone (0.5 mL) were added to a reaction tube equipped with a magnetic dome. After stirring at room temperature for 1 h, TBADT (0.01 mmol), potassium phosphate (0.24 mmol), 26a (0.2 mmol), 1b (1.0 mmol), and trifluorotoluene (0.5 mL) were added. The reaction was carried out under ultraviolet light (10 W, 390 nm) at 25 °C for 60 h. Column chromatography yielded 26c (55.0 mg, 54% yield, dr > 19 / 1).

[0154] 11H NMR (600 MHz, CDCl3) δ 7.54 – 7.46 (m, 2H), 7.47 – 7.39 (m, 2H), 7.36 – 7.27 (m, 3H), 7.25 – 7.05 (m, 2H), 7.01 – 6.94 (m, 1H), 6.89 – 6.74 (m, 1H), 6.08 – 5.10 (m, 1H), 5.09 – 4.91 (m, 1H), 4.37 – 4.28 (m, 1H), 4.26 – 4.09 (m, 1H), 3.73 – 3.64 (m, 1H), 2.92 – 2.64 (m, 3H), 2.41 – 1.77 (m, 4H), 1.58 – 1.45 (m, 6H). 13 13C NMR (151 MHz, CDCl3) δ 172.5, 172.2, 147.0, 146.7, 141.98, 140.8, 138.4, 137.9, 136.3, 135.7, 135.6, 132.5, 132.3, 131.1, 131.0, 130.7, 130.6, 130.3, 130.2, 130.1, 128.12, 128.07, 127.94, 127.93, 127.8, 127.6, 127.5, 127.3, 127.27, 127.25, 126.7, 126.51, 126.49, 126.3, 110.03, 110.00, 77.5, 71.61, 71.56, 58.6, 52.8, 43.1, 42.7, 33.1, 30.1, 20.0, 28.9, 26.6, 25.92, 25.86, 22.6, 21.2. HRMS: (ESI) calcd for C 29 H 30 Cl2NO3 + [M+H] + 510.1597, found 510.1591.

[0155] Example 27

[0156]

[0157] Preparation of protected chiral 1,2-diol 27c: Under an argon atmosphere, E (0.03 mmol), nickel bromide ethylene glycol dimethyl ether (0.02 mmol), and acetone (0.5 mL) were added to a reaction tube equipped with a magnetic dome. After stirring at room temperature for 1 h, TBADT (0.01 mmol), potassium phosphate (0.24 mmol), 27a (0.2 mmol), 1b (1.0 mmol), and trifluorotoluene (0.5 mL) were added. The reaction was carried out under ultraviolet light (10 W, 390 nm) at 25 °C for 60 h. The product 27c (48.2 mg, 67% yield, dr > 19 / 1) was obtained by column chromatography.

[0158] 1 H NMR (600 MHz, CDCl3) δ 8.05 – 8.01 (m, 2H), 7.45 – 7.39 (m, 2H), 5.12 (dd, J = 7.8, 6.3 Hz, 1H), 4.95 – 4.89 (m, 1H), 4.33 (dd, J = 8.3, 6.3Hz, 1H), 3.67 (t, J = 8.0 Hz, 1H), 2.14 – 2.09 (m, 1H), 1.98 – 1.90 (m, 1H), 1.75 – 1.68 (m, 2H), 1.54 (s, 5H), 1.49 (s, 3H), 1.17 – 1.06 (m, 2H), 0.91(t, J = 7.3 Hz, 7H), 0.78 (d, J = 6.9 Hz, 3H). 13 C NMR (151 MHz, CDCl3) δ165.8, 144.4, 130.5, 129.9, 125.9, 110.1, 77.4, 74.9, 71.5, 47.3, 41.0, 34.3,31.5, 26.53, 26.49, 25.9, 23.7, 22.1, 20.8, 16.5. HRMS: (ESI) calcd forC 22 H 33 O4 + [M+H] + 361.2373, found 361.2365.

[0159] Example 28

[0160]

[0161] Preparation of protected chiral 1,2-diol 28c: Under an argon atmosphere, E (0.03 mmol), nickel bromide ethylene glycol dimethyl ether (0.02 mmol), and acetone (0.5 mL) were added to a reaction tube equipped with a magnetic stir bar. After stirring at room temperature for 1 h, TBADT (0.01 mmol), potassium phosphate (0.24 mmol), 28a (0.2 mmol), 1b (1.0 mmol), and trifluorotoluene (0.5 mL) were added. The reaction was carried out under ultraviolet light (10 W, 390 nm) at 25 °C for 60 h. The product 28c (61.6 mg, 65% yield, dr > 19 / 1) was obtained by column chromatography.

[0162] 1 H NMR (600 MHz, CDCl3) δ 8.21 – 8.15 (m, 2H), 7.53 – 7.48 (m, 2H), 7.33 (dd, J = 8.6, 1.1 Hz, 1H), 6.98 (dd, J = 8.5, 2.6 Hz, 1H), 6.94 (d, J =2.5 Hz, 1H), 5.17 (dd, J = 7.7, 6.4 Hz, 1H), 4.37 (dd, J = 8.2, 6.4 Hz, 1H), 3.71 (t, J = 8.0 Hz, 1H), 2.96 – 2.90 (m, 2H), 2.54 – 2.48 (m, 1H), 2.45 –2.40 (m, 1H), 2.35 – 2.28 (m, 1H), 2.18 – 2.11 (m, 1H), 2.09 – 2.00 (m, 2H), 2.00 – 1.95 (m, 1H), 1.66 – 1.60 (m, 2H), 1.59 – 1.43 (m, 10H), 0.92 (s, 3H). 13 C NMR (151 MHz, CDCl3) δ 220.9, 165.2, 148.8, 145.3, 138.1, 137.5, 130.5,129.3, 126.5, 126.1, 121.7, 118.9, 110.2, 77.4, 71.5, 50.5, 48.0, 44.2, 38.0,35.9, 31.6, 29.5, 26.5, 26.4, 25.9, 25.8, 21.6, 13.9. HRMS: (ESI) calcd forC 30 H 35 O5+ [M+H] + 475.2479, found 475.2473.

[0163] Example 29

[0164]

[0165] Preparation of protected chiral 1,2-diol 29c: Under an argon atmosphere, E (0.03 mmol), nickel bromide ethylene glycol dimethyl ether (0.02 mmol), and acetone (0.5 mL) were added to a reaction tube equipped with a magnetic stir bar. After stirring at room temperature for 1 h, TBADT (0.01 mmol), potassium phosphate (0.24 mmol), alkenyl bromide 29a (0.2 mmol), 1b (1.0 mmol), and trifluorotoluene (0.5 mL) were added. The reaction was carried out under ultraviolet light (10 W, 390 nm) at 25 °C for 60 h. Product 29c (16.5 mg, 42% yield, 95% ee) was obtained by column chromatography.

[0166] 1 H NMR (600 MHz, CDCl3) δ 6.13 (q, J = 1.5 Hz, 1H), 4.63 (t, J = 7.0Hz, 1H), 4.23 (dd, J = 8.3, 6.9 Hz, 1H), 3.72 – 3.68 (m, 1H), 2.41 (td, J =6.2, 1.1 Hz, 2H), 2.29 (qd, J = 6.1, 1.6 Hz, 2H), 2.06 – 2.00 (m, 2H), 1.46(s, 3H), 1.42 (s, 3H). 13 C NMR (151 MHz, CDCl3) δ 199.5, 161.7, 124.9, 110.4,77.7, 68.5, 37.8, 26.1, 25.5, 25.4, 22.6. HRMS: (APCI) calcd for C 11 H 17 O3 + [M+H] + 197.1172, found 197.1170.

[0167] Example 30

[0168]

[0169] Preparation of chiral 1,2-diol 1d: Under an argon atmosphere, ethylene glycol (1.0 mmol), silica gel-supported sulfuric acid (1 drop), and acetone (0.5 mL) were added to a reaction tube equipped with a magnetic stir bar. The reaction tube was sealed and stirred at room temperature for 12 h. Calcium chloride powder (0.2 mmol) was then added to quench the reaction. E (0.03 mmol), nickel bromide ethylene glycol dimethyl ether (0.02 mmol), TBADT (0.01 mmol), potassium phosphate (0.24 mmol), 1a (0.2 mmol), acetone (0.5 mL), and trifluorotoluene (0.5 mL) were added. The reaction was carried out under ultraviolet light (10 W, 390 nm) at 25 °C for 60 h. After the light was removed, hydrochloric acid (3 N, 6 mL) was added to the reaction mixture, and the mixture was stirred at room temperature for 6 h. Product 1d (23.4 mg, 65% yield, 90% ee) was obtained by column chromatography.

[0170] 1 H NMR (400 MHz, Methanol-d4) δ 7.95 (d, J = 8.4 Hz, 2H), 7.49 (d, J =8.2 Hz, 2H), 4.73 (dd, J = 6.9, 4.8 Hz, 1H), 4.55 (s, 2H), 3.67 – 3.55 (m,2H), 2.57 (s, 3H). 13 C NMR (151 MHz, Methanol-d4) δ 199.0, 147.9, 136.1, 128.0,126.3, 74.0, 67.1, 25.3.

[0171] Example 31

[0172]

[0173] Preparation of protected chiral 1,3-diol 30c: Under an argon atmosphere, E (0.03 mmol), nickel bromide ethylene glycol dimethyl ether (0.02 mmol), and acetone (0.5 mL) were added to a reaction tube equipped with a magnetic dome. After stirring at room temperature for 1 h, TBADT (0.01 mmol), potassium phosphate (0.3 mmol), 1a (0.2 mmol), 2b (2.0 mmol), and trifluorotoluene (0.5 mL) were added. The reaction was carried out under ultraviolet light (10 W, 390 nm) at 25 °C for 60 h. The product 30c (29.0 mg, 62% yield, 91% ee) was obtained by column chromatography.

[0174] 1H NMR (600 MHz, CDCl3) δ 7.96 – 7.94 (m, 2H), 7.49 – 7.46 (m, 2H), 5.00 (dd, J = 11.7, 2.8 Hz, 1H), 4.15 (td, J = 12.2, 2.7 Hz, 1H), 3.94 (ddd,J = 11.8, 5.3, 1.6 Hz, 1H), 2.60 (s, 3H), 1.90 – 1.81 (m, 1H), 1.75 – 1.67(m, 1H), 1.58 (s, 3H), 1.51 (s, 3H). 13 C NMR (151 MHz, CDCl3) δ 197.8, 147.7,136.4, 128.6, 125.9, 98.9, 70.9, 60.0, 33.4, 30.0, 26.6, 19.2. HRMS: (APCI)calcd for C 14 H 19 O3 + [M+H] + 235.1329, found 235.1320.

[0175] Example 32

[0176]

[0177] Preparation of protected chiral 1,3-diol 31c: Under an argon atmosphere, E (0.03 mmol), nickel bromide ethylene glycol dimethyl ether (0.02 mmol), and acetone (0.5 mL) were added to a reaction tube equipped with a magnetic dome. After stirring at room temperature for 1 h, TBADT (0.01 mmol), potassium phosphate (0.3 mmol), 3a (0.2 mmol), 2b (2.0 mmol), and trifluorotoluene (0.5 mL) were added. The reaction was carried out under ultraviolet light (10 W, 390 nm) at 25 °C for 60 h. The product 31c (21.8 mg, 42% yield, 95% ee) was obtained by column chromatography.

[0178] 1H NMR (600 MHz, CDCl3) δ 7.54 (d, J = 8.0 Hz, 2H), 7.42 (d, J = 8.0Hz, 2H), 4.92 (dd, J = 11.8, 2.7 Hz, 1H), 4.07 (td, J = 12.2, 2.6 Hz, 1H), 3.87 (dd, J = 11.9, 5.2 Hz, 1H), 1.78 (qd, J = 12.5, 5.2 Hz, 1H), 1.65 – 1.60(m, 1H), 1.51 (s, 3H), 1.44 (s, 3H). 13 C NMR (151 MHz, CDCl3) δ 146.4, 129.8(q, J = 32.3 Hz), 126.2, 125.4 (q, J = 3.8 Hz), 124.2 (q, J = 271.9 Hz), 98.9, 70.8, 60.0, 33.4, 30.0, 19.2. 19 F NMR (565 MHz, CDCl3) δ -62.50. HRMS:(ESI) calcd for C 13 H 16 F3O2 + [M+H] + 261.1097, found 261.1102.

[0179] Example 33

[0180]

[0181] Preparation of protected chiral 1,3-diol 32c: Under an argon atmosphere, E (0.03 mmol), nickel bromide ethylene glycol dimethyl ether (0.02 mmol), and acetone (0.5 mL) were added to a reaction tube equipped with a magnetic dome. After stirring at room temperature for 1 h, TBADT (0.01 mmol), potassium phosphate (0.3 mmol), 4a (0.2 mmol), 2b (2.0 mmol), and trifluorotoluene (0.5 mL) were added. The reaction was carried out under ultraviolet light (10 W, 390 nm) at 25 °C for 60 h. The product 32c (21.1 mg, 40% yield, 91% ee) was obtained by column chromatography.

[0182] 1H NMR (600 MHz, CDCl3) δ 7.95 (d, J = 8.2 Hz, 2H), 7.37 (d, J = 8.0Hz, 2H), 4.92 (dd, J = 11.6, 2.7 Hz, 1H), 4.30 (q, J = 7.2 Hz, 2H), 4.07 (td,J = 12.2, 2.5 Hz, 1H), 3.86 (dd, J = 11.9, 5.1 Hz, 1H), 1.78 (qd, J = 12.5,5.2 Hz, 1H), 1.62 – 1.57 (m, 1H), 1.55 (s, 3H), 1.44 (s, 3H), 1.32 (t, J =7.2 Hz, 3H). 13 C NMR (151 MHz, CDCl3) δ 166.5, 147.4, 129.8 129.7 125.7 98.971.0, 61.0, 60.0, 33.4, 30.0, 19.2, 14.3. HRMS: (APCI) calcd for C 15 H 21 O4 + [M+H] + 265.1434, found 265.1434.

[0183] Example 34

[0184]

[0185] Preparation of protected chiral 1,3-diol 33c: Under an argon atmosphere, E (0.03 mmol), nickel bromide ethylene glycol dimethyl ether (0.02 mmol), and acetone (0.5 mL) were added to a reaction tube equipped with a magnetic stir bar. After stirring at room temperature for 1 h, TBADT (0.01 mmol), potassium phosphate (0.3 mmol), 6a (0.2 mmol), 2b (2.0 mmol), and trifluorotoluene (0.5 mL) were added. The reaction was carried out under ultraviolet light (10 W, 390 nm) at 25 °C for 60 h. The product 33c (28.5 mg, 63% yield, 84% ee) was obtained by column chromatography.

[0186] 1H NMR (600 MHz, CDCl3) δ 7.24 (d, J = 1.7 Hz, 4H), 4.83 (dt, J =11.9, 2.2 Hz, 1H), 4.08 – 4.01 (m, 1H), 3.88 – 3.82 (m, 1H), 1.82 – 1.72 (m,1H), 1.62 – 1.55 (m, 1H), 1.50 (s, 3H), 1.42 (s, 3H). 13 C NMR (151 MHz, CDCl3)δ 141.0, 133.2, 128.6, 127.3, 98.9, 70.8, 60.0, 33.5, 30.1, 19.2. HRMS: (APCI) calcd for C 12 H 16 ClO2 + [M+H] + 227.0833, found 227.0827.

[0187] Example 35

[0188]

[0189] Preparation of protected chiral 1,3-diol 34c: Under an argon atmosphere, E (0.03 mmol), nickel bromide ethylene glycol dimethyl ether (0.02 mmol), and acetone (0.5 mL) were added to a reaction tube equipped with a magnetic stir bar. After stirring at room temperature for 1 h, TBADT (0.01 mmol), potassium phosphate (0.3 mmol), 7a (0.2 mmol), 2b (2.0 mmol), and trifluorotoluene (0.5 mL) were added. The reaction was carried out under ultraviolet light (10 W, 390 nm) at 25 °C for 60 h. After concentration, rapid column chromatography was performed to obtain a white solid product 34c (36.7 mg, 68% yield, 92% ee).

[0190] 1H NMR (600 MHz, CDCl3) δ 7.95 – 7.91 (m, 2H), 7.59 (d, J = 8.1 Hz, 2H), 5.03 (dd, J = 11.7, 2.8 Hz, 1H), 4.15 (td, J = 12.2, 2.8 Hz, 1H), 3.95(ddd, J = 11.8, 5.2, 1.6 Hz, 1H), 3.03 (s, 3H), 1.88 – 1.80 (m, 1H), 1.75 –1.70 (m, 1H), 1.58 (s, 3H), 1.51 (s, 3H). 13 C NMR (151 MHz, CDCl3) δ 148.7,139.6, 127.6, 126.8, 99.0, 70.7, 59.9, 44.6, 33.4, 30.0, 19.2. HRMS: (APCI)calcd for C 13 H 19 O4S + [M+H] + 271.0999, found 271.1002.

[0191] Example 36

[0192]

[0193] Preparation of protected chiral 1,3-diol 35c: Under an argon atmosphere, E (0.03 mmol), nickel bromide ethylene glycol dimethyl ether (0.02 mmol), and acetone (0.5 mL) were added to a reaction tube equipped with a magnetic dome. After stirring at room temperature for 1 h, TBADT (0.01 mmol), potassium phosphate (0.3 mmol), 9a (0.2 mmol), 2b (2.0 mmol), and trifluorotoluene (0.5 mL) were added. The reaction was carried out under ultraviolet light (10 W, 390 nm) at 25 °C for 60 h. 35c (21.5 mg, 39% yield, 89% ee) was obtained by column chromatography.

[0194] 1H NMR (600 MHz, CDCl3) δ 7.43 – 7.39 (m, 2H), 7.20 (d, J = 8.3 Hz, 2H), 4.94 (dd, J = 11.7, 2.7 Hz, 1H), 4.13 (td, J = 12.2, 2.7 Hz, 1H), 3.93(ddd, J = 11.9, 5.4, 1.6 Hz, 1H), 1.87 (qd, J = 12.5, 5.3 Hz, 1H), 1.67 (dq,J = 13.2, 2.3 Hz, 1H), 1.58 (s, 3H), 1.50 (s, 3H). 13 C NMR (151 MHz, CDCl3) δ148.5 (q, J = 1.5 Hz), 141.2, 127.4, 121.1, 120.5 (q, J = 256.9 Hz), 98.9,70.8, 60.0, 33.5, 30.1, 19.2. 19 F NMR (565 MHz, CDCl3) δ -57.89. HRMS: (APCI)calcd for C 13 H 16 F3O3 + [M+H] + 277.1046, found 277.1048.

[0195] Example 37

[0196]

[0197] Preparation of protected chiral 1,3-diol 36c: Under an argon atmosphere, E (0.03 mmol), nickel bromide ethylene glycol dimethyl ether (0.02 mmol), and acetone (0.5 mL) were added to a reaction tube equipped with a magnetic stir bar. After stirring at room temperature for 1 h, TBADT (0.01 mmol), potassium phosphate (0.3 mmol), 12a (0.2 mmol), 2b (2.0 mmol), and trifluorotoluene (0.5 mL) were added. The reaction was carried out under ultraviolet light (10 W, 390 nm) at 25 °C for 60 h. The product 36c (28.0 mg, 62% yield, 88% ee) was obtained by column chromatography.

[0198] 1H NMR (600 MHz, CDCl3) δ 7.39 (t, J = 1.9 Hz, 1H), 7.27 – 7.22 (m,3H), 4.91 (dd, J = 11.7, 2.8 Hz, 1H), 4.12 (td, J = 12.2, 2.7 Hz, 1H), 3.93(ddd, J = 11.8, 5.3, 1.6 Hz, 1H), 1.90 – 1.81 (m, 1H), 1.67 (dtd, J = 13.2,2.7, 1.6 Hz, 1H), 1.57 (s, 3H), 1.50 (s, 3H). 13 C NMR (151 MHz, CDCl3) δ 144.5,134.4, 129.7, 127.7, 126.2, 124.0, 98.9, 70.8, 60.0, 33.4, 30.0, 19.2. HRMS: (APCI) calcd for C 12 H 16 ClO2 + [M+H] + 227.0833, found 227.0827.

[0199] Example 38

[0200]

[0201] Preparation of protected chiral 1,3-diol 37c: Under an argon atmosphere, E (0.03 mmol), nickel bromide ethylene glycol dimethyl ether (0.02 mmol), and acetone (0.5 mL) were added to a reaction tube equipped with a magnetic dome. After stirring at room temperature for 1 h, TBADT (0.01 mmol), potassium phosphate (0.3 mmol), 15a (0.2 mmol), 2b (2.0 mmol), and trifluorotoluene (0.5 mL) were added. The reaction was carried out under ultraviolet light (10 W, 390 nm) at 25 °C for 60 h. The product 37c (38.0 mg, 58% yield, 93% ee) was obtained by column chromatography.

[0202] 1H NMR (600 MHz, CDCl3) δ 7.83 (d, J = 1.6 Hz, 2H), 7.79 (s, 1H), 5.06 (dd, J = 11.6, 3.0 Hz, 1H), 4.15 (td, J = 12.1, 2.9 Hz, 1H), 3.96 (ddd, J =11.9, 5.2, 1.7 Hz, 1H), 1.84 (dtd, J = 13.1, 11.9, 5.2 Hz, 1H), 1.76 (dtd, J= 13.2, 2.9, 1.7 Hz, 1H), 1.58 (s, 3H), 1.53 (s, 3H). 13 C NMR (151 MHz, CDCl3) δ 145.0, 131.7 (q, J = 33.2 Hz), 126.1 (q, J = 4.9, 4.1 Hz), 123.3 (q, J =272.5 Hz), 121.5 (p, J = 3.9 Hz), 99.2, 70.2, 59.8, 33.3, 29.9, 19.1. 19 F NMR(575 MHz, CDCl3) δ -62.82. HRMS: (APCI) calcd for C 14 H 15 F6O2 + [M+H] + 329.0971, found 329.0962.

[0203] Example 39

[0204]

[0205] Preparation of protected chiral 1,3-diol 38c: Under an argon atmosphere, E (0.03 mmol), nickel bromide ethylene glycol dimethyl ether (0.02 mmol), and acetone (0.5 mL) were added to a reaction tube equipped with a magnetic dome. After stirring at room temperature for 1 h, TBADT (0.01 mmol), potassium phosphate (0.3 mmol), 17a (0.2 mmol), 2b (2.0 mmol), and trifluorotoluene (0.5 mL) were added. The reaction was carried out under ultraviolet light (10 W, 390 nm) at 25 °C for 60 h. The product 38c (21.3 mg, 43% yield, 95% ee) was obtained by column chromatography.

[0206] 1H NMR (600 MHz, CDCl3) δ 7.82 (d, J = 7.9 Hz, 1H), 7.50 (s, 1H), 7.42 (d, J = 7.8 Hz, 1H), 5.25 (s, 2H), 5.02 – 4.98 (m, 1H), 4.09 (tt, J = 12.2,2.0 Hz, 1H), 3.88 (dd, J = 11.9, 5.2 Hz, 1H), 1.77 (qd, J = 12.3, 5.1 Hz,1H), 1.67 (d, J = 3.3 Hz, 1H), 1.52 (s, 3H), 1.45 (s, 3H). 13 C NMR (151 MHz, CDCl3) δ 171.0, 149.4, 147.2, 126.9, 125.8, 125.0, 119.3, 99.0, 71.0, 69.7,59.9, 33.6, 30.0, 19.2. HRMS: (ESI) calcd for C 14 H 17 O4 + [M+H] + 249.1121, found 249.1123.

[0207] Example 40

[0208]

[0209] Preparation of protected chiral 1,3-diol 38c: Under an argon atmosphere, E (0.03 mmol), nickel bromide ethylene glycol dimethyl ether (0.02 mmol), and acetone (0.5 mL) were added to a reaction tube equipped with a magnetic dome. After stirring at room temperature for 1 h, TBADT (0.01 mmol), potassium phosphate (0.3 mmol), 24a (0.2 mmol), 2b (2.0 mmol), and trifluorotoluene (0.5 mL) were added. The reaction was carried out under ultraviolet light (10 W, 390 nm) at 25 °C for 60 h. The product 38c (57.9 mg, 73% yield, dr > 19 / 1) was obtained by column chromatography.

[0210] 1H NMR (600 MHz, CDCl3) δ 7.71 (d, J = 8.1 Hz, 2H), 7.42 (d, J = 8.1Hz, 2H), 7.31 – 7.22 (m, 3H), 7.14 – 7.09 (m, 2H), 6.59 (d, J = 7.6 Hz, 1H),5.11 – 5.05 (m, 1H), 4.97 (dd, J = 11.7, 2.8 Hz, 1H), 4.16 – 4.10 (m, 1H), 3.95 – 3.90 (m, 1H), 3.76 (s, 3H), 3.29 (dd, J = 13.9, 5.8 Hz, 1H), 3.21 (dd,J = 13.9, 5.4 Hz, 1H), 1.89 – 1.80 (m, 1H), 1.71 – 1.65 (m, 1H), 1.57 (s, 3H), 1.50 (s, 3H). 13 C NMR (151 MHz, CDCl3) δ 172.1, 166.6, 146.4, 135.9,133.1, 129.3, 128.6, 127.2, 126.0, 98.9, 70.9, 60.0, 53.5, 52.4, 37.9, 33.4,30.0, 19.2. HRMS: (ESI) calcd for C 23 H 28 NO5 + [M+H] + 398.1962, found 398.1961.

[0211] Example 41

[0212]

[0213] Preparation of protected chiral 1,3-diol 39c: Under an argon atmosphere, E (0.03 mmol), nickel bromide ethylene glycol dimethyl ether (0.02 mmol), and acetone (0.5 mL) were added to a reaction tube equipped with a magnetic dome. After stirring at room temperature for 1 h, TBADT (0.01 mmol), potassium phosphate (0.3 mmol), 26a (0.2 mmol), 2b (2.0 mmol), and trifluorotoluene (0.5 mL) were added. The reaction was carried out under ultraviolet light (10 W, 390 nm) at 25 °C for 60 h. The product 39c (68.4 mg, 58% yield, dr > 19 / 1) was obtained by column chromatography.

[0214] 1 H NMR (600 MHz, CDCl3) δ 8.03 – 8.00 (m, 2H), 7.45 – 7.42 (m, 2H),5.42 (dd, J = 5.0, 2.1 Hz, 1H), 4.99 (dd, J = 11.7, 2.8 Hz, 1H), 4.85 (dtd, J= 16.3, 8.4, 4.5 Hz, 1H), 4.14 (td, J = 12.2, 2.7 Hz, 1H), 3.93 (ddd, J =11.8, 5.3, 1.6 Hz, 1H), 2.47 – 2.44 (m, 2H), 2.04 – 1.96 (m, 3H), 1.91 (dt, J= 13.4, 3.6 Hz, 1H), 1.84 (tdd, J = 12.8, 10.3, 5.4 Hz, 2H), 1.75 – 1.71 (m,1H), 1.71 – 1.67 (m, 1H), 1.59 – 1.45 (m, 12H), 1.40 – 1.31 (m, 3H), 1.28 –1.09 (m, 8H), 1.07 (s, 3H), 1.03 – 0.96 (m, 3H), 0.92 (d, J = 6.5 Hz, 3H),0.87 (d, J = 2.8 Hz, 3H), 0.86 (d, J = 2.8 Hz, 3H), 0.69 (s, 3H). 13 C NMR (151MHz, CDCl3) δ 165.8, 147.4, 139.7, 130.0, 129.8, 125.6, 122.8, 98.9, 74.6,71.0, 60.0, 56.7, 56.2, 50.1, 42.3, 39.8, 39.5, 38.2, 37.0, 36.7, 36.2, 35.8,33.5, 32.0, 31.9, 30.0, 28.3, 28.0, 27.9, 24.3, 23.8, 22.9, 22.6, 21.1, 19.4,19.2, 18.7, 11.9. HRMS: (APCI) calcd for C 40 H 61 O4 + [M+H] + 605.4564, found605.4558.

[0215] Example 42

[0216]

[0217] Preparation of protected chiral 1,3-diol 40c: Under an argon atmosphere, E (0.03 mmol), nickel bromide ethylene glycol dimethyl ether (0.02 mmol), and acetone (0.5 mL) were added to a reaction tube equipped with a magnetic ball. After stirring at room temperature for 1 h, TBADT (0.01 mmol), potassium phosphate (0.3 mmol), 27a (0.2 mmol), 2b (2.0 mmol), and trifluorotoluene (0.5 mL) were added. The reaction was carried out under ultraviolet light (10 W, 390 nm) at 25 °C for 60 h. 40c was obtained by column chromatography (46.4 mg, 62% yield, dr > 19 / 1).

[0218] 1 H NMR (600 MHz, CDCl3) δ 8.05 – 8.00 (m, 2H), 7.46 – 7.42 (m, 2H), 4.98 (dd, J = 11.7, 2.8 Hz, 1H), 4.94 – 4.89 (m, 1H), 4.16 – 4.10 (m, 1H),3.95 – 3.90 (m, 1H), 2.15 – 2.08 (m, 1H), 1.97 – 1.90 (m, 1H), 1.89 – 1.80(m, 1H), 1.75 – 1.66 (m, 3H), 1.60 – 1.52 (m, 5H), 1.50 (s, 3H), 1.16 – 1.05(m, 2H), 0.91 (dd, J = 9.9, 6.8 Hz, 7H), 0.78 (d, J = 6.9 Hz, 3H). 13 C NMR (151MHz, CDCl3) δ 165.9, 147.3, 130.1, 129.8, 125.7, 98.9, 74.8, 70.9, 60.0,47.3, 41.0, 34.3, 33.4, 31.5, 30.0, 26.6, 23.7, 22.1, 20.8, 19.2, 16.6. HRMS:(APCI) calcd for C 23 H 35 O4 + [M+H] + 375.2529, found 375.2522.

[0219] Example 43

[0220]

[0221] Preparation of protected chiral 1,3-diol 41c: Under an argon atmosphere, E (0.03 mmol), nickel bromide ethylene glycol dimethyl ether (0.02 mmol), and acetone (0.5 mL) were added to a reaction tube equipped with a magnetic dome. After stirring at room temperature for 1 h, TBADT (0.01 mmol), potassium phosphate (0.3 mmol), 28a (0.2 mmol), 2b (2.0 mmol), and trifluorotoluene (0.5 mL) were added. The reaction was carried out under ultraviolet light (10 W, 390 nm) at 25 °C for 60 h. The product 46c (45.9 mg, 47% yield, dr > 19 / 1) was obtained by column chromatography.

[0222] 1 H NMR (600 MHz, CDCl3) δ 8.17 (d, J = 8.0 Hz, 2H), 7.51 (d, J = 8.0Hz, 2H), 7.33 (d, J = 8.5 Hz, 1H), 6.98 (dd, J = 8.5, 2.6 Hz, 1H), 6.94 (d, J= 2.5 Hz, 1H), 5.03 (dd, J = 11.8, 2.8 Hz, 1H), 4.16 (td, J = 12.1, 2.6 Hz,1H), 3.97 – 3.93 (m, 1H), 2.97 – 2.92 (m, 2H), 2.52 (dd, J = 19.1, 8.8 Hz,1H), 2.46 – 2.41 (m, 1H), 2.32 (td, J = 11.0, 4.2 Hz, 1H), 2.16 (dt, J =18.6, 8.8 Hz, 2H), 2.10 – 2.00 (m, 3H), 1.98 (dt, J = 12.9, 3.1 Hz, 1H), 1.87(qd, J = 12.5, 5.2 Hz, 1H), 1.75 – 1.71 (m, 1H), 1.62 – 1.51 (m, 10H), 0.93(s, 3H). 13C NMR (151 MHz, CDCl3) δ 220.8, 165.3, 148.8, 148.3, 138.1, 137.4,130.4, 128.8, 126.5, 125.9, 121.7, 118.9, 99.0, 70.9, 60.0, 50.5, 48.0, 44.2,38.0, 35.9, 33.5, 31.6, 30.0, 29.4, 26.4, 25.8, 21.6, 19.2, 13.9. HRMS:(APCI) calcd for C 31 H 37 O5 + [M+H] + 489.2636, found 489.2631.

[0223] Example 44

[0224]

[0225] Preparation of protected chiral 1,3-diol 42c: Under an argon atmosphere, E (0.03 mmol), nickel bromide ethylene glycol dimethyl ether (0.02 mmol), and acetone (0.5 mL) were added to a reaction tube equipped with a magnetic dome. After stirring at room temperature for 1 h, TBADT (0.01 mmol), potassium phosphate (0.3 mmol), 29a (0.2 mmol), 2b (2.0 mmol), and trifluorotoluene (0.5 mL) were added. The reaction was carried out under ultraviolet light (10 W, 390 nm) at 25 °C for 60 h. The product 42c (21.4 mg, 51% yield, 97% ee) was obtained by column chromatography.

[0226] 1H NMR (600 MHz, CDCl3) δ 6.11 (s, 1H), 4.45 (dt, J = 12.0, 2.0 Hz,1H), 4.04 (td, J = 12.1, 2.8 Hz, 1H), 3.90 (ddd, J = 11.9, 5.4, 1.7 Hz, 1H), 2.40 (t, J = 6.7 Hz, 2H), 2.35 (dtd, J = 12.5, 6.2, 1.6 Hz, 1H), 2.32 – 2.26(m, 1H), 2.01 (q, J = 6.4 Hz, 2H), 1.72 (dd, J = 12.3, 5.3 Hz, 1H), 1.60 (dq,J = 13.1, 2.4 Hz, 1H), 1.49 (s, 3H), 1.43 (s, 3H). 13 C NMR (151 MHz, CDCl3) δ199.9, 163.9, 124.1, 98.7, 71.0, 59.7, 37.8, 29.8, 29.7, 25.6, 22.6, 19.1.HRMS: (APCI) calcd for C 12 H 19 O2 + [M+H] + 211.1329, found 211.1328.

[0227] Example 45

[0228]

[0229] Preparation of chiral 1,3-diol 36d: 36c (0.124 mmol) and hydrochloric acid (2 mL, 2 M inMeOH) were added to a flask and stirred at room temperature for 3 h. The product 36d (20.8 mg, 90% yield, 89% ee) was obtained by column chromatography.

[0230] 1 H NMR (600 MHz, CDCl3) δ 7.38 (s, 1H), 7.31 – 7.19 (m, 4H), 5.00 –4.91 (m, 1H), 3.88 (t, J = 5.2 Hz, 2H), 2.58 (s, 3H), 2.05 – 1.90 (m, 2H). 13CNMR (151 MHz, CDCl3) δ 146.4, 134.4, 129.8, 127.6, 125.9, 123.8, 73.7, 61.4,40.4.

[0231] Example 46

[0232]

[0233] Preparation of chiral 1,3-diol 4d: Under an argon atmosphere, 1,3-propanediol (1.0 mmol), silica gel-supported sulfuric acid (1 drop), and acetone (0.5 mL) were added to a reaction tube equipped with a magnetic dome. The reaction tube was sealed and stirred at room temperature for 12 h. Calcium chloride powder (0.2 mmol) was then added to quench the reaction. E (0.03 mmol), nickel bromide ethylene glycol dimethyl ether (0.02 mmol), TBADT (0.01 mmol), potassium phosphate (0.4 mmol), 1a (0.2 mmol), acetone (1 mL), and trifluorotoluene (1 mL) were added. The reaction was carried out under ultraviolet light (10 W, 390 nm) at 25 °C for 60 h. After the light was removed, hydrochloric acid (3 N, 6 mL) was added to the reaction mixture, and the mixture was stirred at room temperature for 6 h. The product 4d (24.0 mg, 62% yield, 89% ee) was obtained by column chromatography.

[0234] 1 H NMR (400 MHz, CDCl3) δ 7.94 – 7.89 (m, 2H), 7.44 (d, J = 8.2 Hz, 2H), 5.02 (dd, J = 7.2, 5.1 Hz, 1H), 3.86 (t, J = 5.5 Hz, 2H), 2.82 (s, 2H), 2.58 (s, 3H), 1.99 – 1.91 (m, 2H). 13 C NMR (151 MHz, CDCl3) δ 198.1, 149.8,136.2, 128.6, 125.7, 73.7, 61.2, 40.2, 26.6.

[0235] Comparative Example 1

[0236]

[0237] Under an argon atmosphere, E (0.03 mmol), nickel bromide ethylene glycol dimethyl ether (0.02 mmol), TBADT (0.01 mmol), potassium phosphate (0.24 mmol), 1a (0.2 mmol), 1b (1.0 mmol), trifluorotoluene (0.5 mL), and acetone (0.5 mL) were added to a reaction tube containing a magnetic dome. The reaction was carried out at 25 °C for 60 h under ultraviolet light (10 W, 390 nm). Product 1e (28 mg, 58% yield, 48% ee) was obtained by column chromatography.

[0238] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A method for synthesizing a chiral diol, characterized in that, The chiral diol is a chiral 1,2-diol or a chiral 1,3-diol; the chiral diol is synthesized using any one of the following two methods; Method I includes the following steps: under an inert atmosphere, the ligand, nickel catalyst and organic solvent are mixed for 1-2 h, a photocatalyst, a base, a bromide, and a diol precursor are added, and the mixture is reacted under ultraviolet light at 25 °C to obtain a protected chiral diol. The protected chiral diol is then deprotected to obtain a chiral diol. Method II includes the following steps: under an inert atmosphere, ethylene glycol or 1,3-propanediol is first subjected to a protective reaction, followed by the addition of a ligand, a nickel catalyst, a photocatalyst, a base, a bromide, and an organic solvent, and the reaction is continued at 25 °C under ultraviolet light irradiation to obtain a chiral glycol; the protective reaction is as follows: under acidic conditions, ethylene glycol or 1,3-propanediol reacts with acetone to obtain protected ethylene glycol or 1,3-propanediol; The brominated product is selected from one of the following structures: ； The ligand is (4) R ,4' R )-2,2'-(propane-2,2-diyl)bis(5,5-dimethyl-4-phenyl-4,5-dihydrooxazole); The photocatalyst is tetrabutylammonium decatungstate; The nickel catalyst is nickel bromide ethylene glycol dimethyl ether; The diol precursor is selected from one of the following structures: 。 2. The method for synthesizing a chiral diol according to claim 1, characterized in that, The molar ratio of the brominated product, diol precursor, nickel catalyst, ligand, photocatalyst, and base is 1: (5~10): 0.1: 0.15: 0.05: (1.2~1.5), wherein the concentration of the brominated product is 0.1~0.2 mol / L.

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