Synthesis method of chiral diol

Abstract

The invention discloses a synthesis method of chiral diol, and belongs to the technical field of organic synthesis. The chiral diol is chiral 1, 2-diol or 1, 3-diol. The preparation method comprises the following steps: by taking a bromide (aryl bromide or alkenyl bromide) and a diol precursor as substrates, in the presence of a ligand, a photocatalyst and a nickel catalyst, reacting under the irradiation of purple light to obtain protected chiral diol, and then performing deprotection to obtain the chiral diol, or the chiral diol is synthesized from ethylene glycol or 1, 3-propylene glycol through a one-pot method. According to the present invention, the light / nickel concerted catalysis strategy is adopted, the stereoselective arylation or alkenylation reaction of the 1, 2-diol or the 1, 3-diol oxygen ortho-position C (sp3)-H bond is achieved, the reaction conditions are mild, and the substrate adaptability is wide. According to the chiral 1, 2-diol or 1, 3-diol prepared by the method disclosed by the invention, synthesis of various natural products, commercially available drugs and chiral ligands can be realized through subsequent conversion, and the chiral 1, 2-diol or 1, 3-diol has a huge synthesis value.

Description

Technical Field

[0001] The invention relates to the technical field of organic synthesis, and in particular to a method for synthesizing chiral diols. Background Art

[0002] Chiral diols are widely present in drug molecules and natural products and are an important class of molecular structures. According to statistics, among the top 200 small molecule drugs in terms of sales in 2022, 20% of the best-selling drugs contain chiral diol structural units. Among them, chiral 1,2-diols and 1,3-diols are also important intermediates for the synthesis of various chiral catalysts, drugs, natural products and fine chemicals, and have a wide range of applications in organic synthesis.

[0003] However, the synthesis of chiral 1,2-diols or 1,3-diols in the past relied on asymmetric dihydroxylation of olefins, asymmetric reduction of carbonyl compounds, or asymmetric splitting, which faced disadvantages such as high reaction cost, difficult preparation of raw materials, low substrate universality, and poor atom economy. Summary of the invention

[0004] In view of the above deficiencies in the prior art, the present invention provides a method for synthesizing chiral diols, which utilizes light-promoted hydrogen atom transfer and nickel-synergistic catalytic strategies to directly break the carbon-hydrogen bonds of the diol precursors to achieve enantioselective arylation and olefination, and prepare a series of chiral diols. The synthesized chiral diols can be used to synthesize a variety of commercially available drugs through subsequent transformations, and have great synthetic value.

[0005] To achieve the above purpose, the specific technical solutions of the present invention are 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 by one of the following two methods;

[0007] Method I comprises the following steps: under an inert atmosphere, mixing a ligand, a nickel catalyst and an organic solvent for 1 to 2 hours, adding a photocatalyst, a base, a bromide and a diol precursor, reacting at 25° C. for 48 to 80 hours under ultraviolet light irradiation to obtain a protected chiral diol, and deprotecting the protected chiral diol to obtain a chiral diol;

[0008] Method II comprises the following steps: firstly, in an inert atmosphere, performing a protection reaction on ethylene glycol or 1,3-propylene glycol, then adding a ligand, a nickel catalyst, a photocatalyst, a base, a bromide, and an organic solvent, and continuing the reaction at 25° C. for 48 to 80 hours under ultraviolet light to obtain a chiral diol;

[0009] The bromide 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) (ie, the structure shown in E).

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

[0014]

[0015] Further preferably, the photocatalyst is tetrabutylammonium decatungstate (TBADT for short, 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 dimethyl ether, nickel bromide dimethyl ether, cyclooctadiene nickel, nickel acetylacetonate, nickel perchlorate, nickel iodide or nickel acetate tetrahydrate.

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

[0018] Preferably, the bromide 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-dioxolane (ie, the structure shown in 1b) or 2,2-dimethyl-1,3-dioxane (ie, the structure shown in 2b).

[0023] Preferably, 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-lutidine.

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

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

[0026] Preferably, the molar ratio of the bromide, 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 bromide is 0.1-0.2 mol / L.

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

[0028] The present invention uses bromide (aryl bromide or alkenyl bromide) and diol precursor as substrates, and utilizes visible light-promoted hydrogen atom transfer (HAT) process to directly break the carbon-hydrogen bond of the diol precursor to generate oxygen-ortho free radicals, and then under the coordinated catalysis of a chiral nickel catalyst, with a specific ligand, it is coupled with the bromide (aryl bromide or alkenyl bromide) to obtain a protected chiral diol with high optical purity, and the protected chiral diol is deprotected to obtain a chiral diol; the present invention utilizes the light / nickel coordinated catalysis strategy to achieve stereoselective arylation and alkenylation of the oxygen-ortho carbon-hydrogen bond of the diol precursor. The chiral diol prepared by the method of the present invention can realize the synthesis of a variety of natural products, commercially available drugs and chiral ligands through subsequent transformation, and has great synthetic value.

[0029] Compared with the prior art, the present invention is beneficial in that:

[0030] 1. The present invention provides a strategy of utilizing photo-promoted hydrogen atom transfer and nickel synergistic catalysis. Method I directly breaks the carbon-hydrogen bond of the diol precursor to achieve enantioselective arylation and olefination to prepare a series of chiral diols; Method II starts from cheap and readily available ethylene glycol or 1,3-propylene glycol to synthesize chiral diols with high optical purity in one pot. 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 the present invention has mild reaction conditions, good functional group tolerance, and a wide range of substrate applications. It is an efficient, green, and inexpensive method for synthesizing chiral diols. DETAILED DESCRIPTION

[0032] The technical solution of the present invention will be described clearly and completely below. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0033] The present 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 by one of the following two methods:

[0034] Method I comprises the following steps: under an inert atmosphere, mixing a ligand, a nickel catalyst and an organic solvent for 1 to 2 hours, adding a photocatalyst, a base, a bromide and a diol precursor, reacting at 25° C. for 48 to 80 hours under ultraviolet light irradiation to obtain a protected chiral diol, and deprotecting the protected chiral diol to obtain a chiral diol;

[0035] Method II comprises the following steps: firstly, in an inert atmosphere, performing a protection reaction on ethylene glycol or 1,3-propylene glycol, then adding a ligand, a nickel catalyst, a photocatalyst, a base, a bromide, and an organic solvent, and continuing the reaction at 25° C. for 48 to 80 hours under ultraviolet light to obtain a chiral diol;

[0036] The bromide 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 dimethyl ether, nickel bromide dimethyl ether, cyclooctadiene nickel, nickel acetylacetonate, nickel perchlorate, nickel iodide, or nickel acetate tetrahydrate.

[0042] In some examples, the bromide 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 by using existing technology or can be 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-lutidine.

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

[0049] In some examples, the molar ratio of the bromide, 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 bromide is 0.1-0.2 mol / L.

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

[0051] Example 1

[0052]

[0053] Preparation of protected chiral 1, 2-diol 1c: Under 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 magnet. 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 mixture was reacted at 25 °C under irradiation with a violet lamp (10 W, 390 nm) for 60 h. The 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 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 magnet. 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 mixture was reacted at 25 °C under irradiation with a violet lamp (10 W, 390 nm) for 60 h. The 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, found 204.1014.

[0059] Example 3

[0060]

[0061] Preparation of protected chiral 1, 2-diol 3c: Under 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 magnet. 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 mixture was reacted at 25 °C under irradiation with a violet lamp (10 W, 390 nm) for 60 h. The 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 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 magnet. 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 and reacted at 25 °C under irradiation with a purple lamp (10 W, 390 nm) 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 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 magnet. 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 mixture was reacted at 25 °C under irradiation with a purple lamp (10 W, 390 nm) 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 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 magnet. 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 and reacted at 25 °C under irradiation with a purple lamp (10 W, 390 nm) 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 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 magnet. 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 and reacted at 25 °C under irradiation with a purple lamp (10 W, 390 nm) 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 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 magnet. 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 and reacted at 25 °C under irradiation with a purple lamp (10 W, 390 nm) 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 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 magnet. 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 and reacted at 25 °C under irradiation with a purple lamp (10 W, 390 nm) 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 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 magnet. 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 mixture was reacted at 25 °C under irradiation with a violet lamp (10 w, 390 nm) 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] Embodiment 11

[0092]

[0093] Preparation of protected chiral 1, 2-diol 11c: Under 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 magnet. 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 and reacted at 25 °C under irradiation with a purple lamp (10 W, 390 nm) 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 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 magnet. 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 mixture was reacted at 25 °C under irradiation with a violet lamp (10 W, 390 nm) for 60 h. After concentration and flash column chromatography, the product 12c (27.1 mg, 64% yield, 89% ee) was obtained.

[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 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 magnet. 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 and reacted at 25 °C under irradiation with a purple lamp (10 W, 390 nm) 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, found237.1126.

[0103] Embodiment 14

[0104]

[0105] Preparation of protected chiral 1, 2-diol 14c: Under 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 magnet. 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 mixture was reacted at 25 °C under irradiation with a violet lamp (10 W, 390 nm) 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] Embodiment 15

[0108]

[0109] Preparation of protected chiral 1, 2-diol 15c: Under 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 magnet. 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 mixture was reacted at 25 °C under irradiation with a violet lamp (10 W, 390 nm) 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 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 magnet. 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 mixture was reacted at 25 °C under irradiation with a violet lamp (10 W, 390 nm) 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, found317.0988.

[0115] Embodiment 17

[0116]

[0117] Preparation of protected chiral 1, 2-diol 17c: Under 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 magnet. 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 and reacted at 25 °C for 60 h under irradiation with a violet lamp (10 W, 390 nm); 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] Embodiment 18

[0120]

[0121] Preparation of protected chiral 1, 2-diol 18c: Under 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 magnet. 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 mixture was reacted at 25 °C under irradiation with a violet lamp (10 W, 390 nm) 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] Embodiment 19

[0124]

[0125] Preparation of protected chiral 1, 2-diol 19c: Under 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 magnet. 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 mixture was reacted at 25 °C under irradiation with a violet lamp (10 W, 390 nm) 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] Embodiment 20

[0128]

[0129] Preparation of protected chiral 1, 2-diol 20c: Under 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 magnet. 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 mixture was reacted at 25 °C under irradiation with a violet lamp (10 W, 390 nm) 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 O2S + [M+Na] + 307.0763, found 307.0763.

[0131] Embodiment 21

[0132]

[0133] Preparation of protected chiral 1, 2-diol 21c: Under 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 magnet. 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 mixture was reacted at 25 °C under irradiation with a purple lamp (10 W, 390 nm) 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 O2S + [M+Na] + 257.0607, found 257.0609.

[0135] Embodiment 22

[0136]

[0137] Preparation of protected chiral 1, 2-diol 22c: Under 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 magnet. 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 mixture was reacted at 25 °C under irradiation with a violet lamp (10 W, 390 nm) 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, found248.0887.

[0139] Embodiment 23

[0140]

[0141] Preparation of protected chiral 1, 2-diol 23c: Under 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 magnet. 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 mixture was reacted at 25 °C under irradiation with a violet lamp (10 W, 390 nm) 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] Embodiment 24

[0144]

[0145] Preparation of protected chiral 1, 2-diol 24c: Under 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 magnet. 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 mixture was reacted at 25 °C under irradiation with a violet lamp (10 W, 390 nm) for 60 h. After column chromatography, the product 24c (55.2 mg, 72% yield, dr > 19 / 1) was obtained.

[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] Embodiment 25

[0148]

[0149] Preparation of protected chiral 1, 2-diol 25c: Under 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 magnet. 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 mixture was reacted at 25 °C under irradiation with a violet lamp (10 W, 390 nm) 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] Embodiment 26

[0152]

[0153] Preparation of protected chiral 1, 2-diol 26c: Under 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 magnet. 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 mixture was reacted at 25 °C under irradiation with a violet lamp (10 W, 390 nm) for 60 h. 26c (55.0 mg, 54% yield, dr > 19 / 1) was obtained by column chromatography.

[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 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 magnet. 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 mixture was reacted at 25 °C under irradiation with a violet lamp (10 W, 390 nm) 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] Embodiment 28

[0160]

[0161] Preparation of protected chiral 1, 2-diol 28c: Under 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 magnet. 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 mixture was reacted at 25 °C under irradiation with a violet lamp (10 W, 390 nm) 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] Embodiment 29

[0164]

[0165] Preparation of protected chiral 1, 2-diol 29c: Under 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 magnet. 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 mixture was reacted at 25 °C under irradiation with a violet lamp (10 W, 390 nm) for 60 h. The 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] Embodiment 30

[0168]

[0169] Preparation of chiral 1, 2-diol 1d: Under argon atmosphere, ethylene glycol (1.0 mmol), silica-supported sulfuric acid (1 drop) and acetone (0.5 mL) were added to a reaction tube equipped with a magnet. The reaction tube was sealed and stirred at room temperature for 12 h. Calcium chloride powder (0.2 mmol) was added to quench the reaction. E (0.03 mmol), nickel bromide 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 at 25 °C under irradiation with a violet lamp (10 W, 390 nm) for 60 h. The irradiation was stopped, and hydrochloric acid (3 N, 6 mL) was added to the reaction mixture. The reaction was stirred at room temperature for 6 h. The 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] Embodiment 31

[0172]

[0173] Preparation of protected chiral 1, 3-diol 30c: Under 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 magnet. 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 mixture was reacted at 25 °C under irradiation with a violet lamp (10 W, 390 nm) 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] Embodiment 32

[0176]

[0177] Preparation of protected chiral 1, 3-diol 31c: Under 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 magnet. 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 mixture was reacted at 25 °C under irradiation with a purple lamp (10 W, 390 nm) 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] Embodiment 33

[0180]

[0181] Preparation of protected chiral 1, 3-diol 32c: Under 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 magnet. 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 mixture was reacted at 25 °C under irradiation with a violet lamp (10 W, 390 nm) 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] Embodiment 34

[0184]

[0185] Preparation of protected chiral 1, 3-diol 33c: Under 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 magnet. 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 mixture was reacted at 25 °C under irradiation with a violet lamp (10 W, 390 nm) 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] Embodiment 35

[0188]

[0189] Preparation of protected chiral 1, 3-diol 34c: Under 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 magnet. 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 mixture was reacted at 25 °C under irradiation with a violet lamp (10 W, 390 nm) for 60 h. After concentration and flash column chromatography, a white solid product 34c (36.7 mg, 68% yield, 92% ee) was obtained.

[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] Embodiment 36

[0192]

[0193] Preparation of protected chiral 1, 3-diol 35c: Under 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 magnet. 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 mixture was reacted at 25 °C under irradiation with a violet lamp (10 W, 390 nm) 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] Embodiment 37

[0196]

[0197] Preparation of protected chiral 1, 3-diol 36c: Under 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 magnet. 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 mixture was reacted at 25 °C under irradiation with a violet lamp (10 W, 390 nm) 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] Embodiment 38

[0200]

[0201] Preparation of protected chiral 1, 3-diol 37c: Under 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 magnet. 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 mixture was reacted at 25 °C under irradiation with a violet lamp (10 W, 390 nm) 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] Embodiment 39

[0204]

[0205] Preparation of protected chiral 1, 3-diol 38c: Under 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 magnet. 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 mixture was reacted at 25 °C under irradiation with a violet lamp (10 W, 390 nm) 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, found249.1123.

[0207] Embodiment 40

[0208]

[0209] Preparation of protected chiral 1, 3-diol 38c: Under 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 magnet. 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 mixture was reacted at 25 °C under irradiation with a violet lamp (10 W, 390 nm) 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] Embodiment 41

[0212]

[0213] Preparation of protected chiral 1, 3-diol 39c: Under 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 magnet. 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 mixture was reacted at 25 °C under irradiation with a violet lamp (10 W, 390 nm) 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] Embodiment 42

[0216]

[0217] Preparation of protected chiral 1, 3-diol 40c: Under 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 magnet. 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 mixture was reacted at 25 °C under irradiation with a violet lamp (10 W, 390 nm) for 60 h. 40c (46.4 mg, 62% yield, dr > 19 / 1) was obtained by column chromatography.

[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] Embodiment 43

[0220]

[0221] Preparation of protected chiral 1, 3-diol 41c: Under 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 magnet. 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 mixture was reacted at 25 °C under irradiation with a violet lamp (10 W, 390 nm) 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] Embodiment 44

[0224]

[0225] Preparation of protected chiral 1, 3-diol 42c: Under 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 magnet. 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 mixture was reacted at 25 °C under irradiation with a violet lamp (10 W, 390 nm) for 60 h. After column chromatography, the product 42c (21.4 mg, 51% yield, 97% ee) was obtained.

[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] Embodiment 45

[0228]

[0229] Preparation of chiral 1, 3-diol 36d: 36c (0.124 mmol) and hydrochloric acid (2 mL, 2M 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] Embodiment 46

[0232]

[0233] Preparation of chiral 1, 3-diol 4d: Under argon atmosphere, 1,3-propanediol (1.0 mmol), silica-supported sulfuric acid (1 drop) and acetone (0.5 mL) were added to a reaction tube equipped with a magnet. The reaction tube was sealed and stirred at room temperature for 12 h. Calcium chloride powder (0.2 mmol) was added to quench the reaction. E (0.03 mmol), nickel bromide 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 at 25 °C under irradiation with a violet lamp (10 W, 390 nm) for 60 h. The illumination was stopped, and hydrochloric acid (3 N, 6 mL) was added to the reaction mixture. The reaction 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 argon atmosphere, E (0.03 mmol), nickel bromide 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 equipped with a magnet and reacted at 25 ℃ for 60 h under irradiation with a purple lamp (10 W, 390 nm). The product 1e (28 mg, 58% yield, 48% ee) was obtained by column chromatography.

[0238] Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention 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 by any one of the following two methods; Method I comprises the following steps: under an inert atmosphere, mixing a ligand, a nickel catalyst and an organic solvent for 1 to 2 hours, adding a photocatalyst, a base, a bromide and a diol precursor, reacting at 25° C. under ultraviolet light irradiation to obtain a protected chiral diol, and deprotecting the protected chiral diol to obtain a chiral diol; Method II comprises the following steps: firstly, in an inert atmosphere, performing a protection reaction on ethylene glycol or 1,3-propylene glycol, then adding a ligand, a nickel catalyst, a photocatalyst, a base, a bromide, and an organic solvent, and continuing the reaction at 25° C. under ultraviolet light to obtain a chiral diol; The bromide is an aryl bromide or an alkenyl bromide.

2. The method for synthesizing a chiral diol according to claim 1, characterized in that: The ligand is selected from one of the following structures: 。 3. The method for synthesizing a chiral diol according to claim 2, characterized in that: The ligand is (4R, 4'R)-2,2'-(propane-2,2-diyl)bis(5,5-dimethyl-4-phenyl-4,5-dihydrooxazole).

4. The method for synthesizing a chiral diol according to claim 1, characterized in that: The photocatalyst is selected from one of the following structures: 。 5. The method for synthesizing a chiral diol according to claim 4, characterized in that: The photocatalyst is tetrabutylammonium decatungstate.

6. The method for synthesizing a chiral diol according to claim 1, characterized in that: The nickel catalyst includes but is not limited to one of nickel chloride, nickel bromide, nickel chloride dimethyl ether, nickel bromide dimethyl ether, cyclooctadiene nickel, nickel acetylacetonate, nickel perchlorate, nickel iodide, and nickel acetate tetrahydrate.

7. The method for synthesizing a chiral diol according to claim 6, characterized in that: The nickel catalyst is nickel bromide ethylene glycol dimethyl ether.

8. The method for synthesizing a chiral diol according to claim 1, characterized in that: The bromide is selected from one of the following structures: 。 9. The method for synthesizing a chiral diol according to claim 1, characterized in that: The diol precursor is selected from one of the following structures: 。 10. The method for synthesizing a chiral diol according to claim 1, characterized in that: The molar ratio of the bromide, 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 bromide is 0.1-0.2 mol / L.

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