COMPOUND AND PREPARATION METHOD AND APPLICATION THEREOF

Abstract

The present disclosure relates to a compound and a preparation method and application thereof, the compound having a chemical structure formula of:

##STR00001##

wherein M in the formula is selected from a group consisting of CF.sub.3 or CF.sub.2H, and R.sub.1, R.sub.2, and R.sub.3 are each independently selected from a group consisting of aryl, heteroaryl, and alkyl. The compound provided by the present disclosure can be used as a trifluoroethanolation reagent or difluoroethanolation reagent as synthetic intermediates of many organic compounds, and some of the compounds have pharmaceutical activity. The preparation steps of such compounds are simplified, with mild synthesis conditions and wide applicability of substrates.

Claims

1. A compound, having a chemical structure formula of: ##STR00046## wherein M is selected from a group consisting of CF.sub.3 or CF.sub.2H, R.sub.1 is selected from a group consisting of aryl, heteroaryl, and alkyl, R.sub.2 is selected from a group consisting of aryl, heteroaryl, and alkyl, and R.sub.3 is selected from a group consisting of aryl, heteroaryl, and alkyl.

2. The compound according to claim 1, wherein, the aryl is selected from a group consisting of phenyl, biphenyl, naphthyl, terphenyl, anthracenyl, and substituted aryl.

3. The compound according to claim 1, wherein, the heteroaryl is selected from a group consisting of pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazinyl, furanyl, thienyl, imidazolyl, triazolyl, tetrazolyl, thiazolyl, isothiazolyl, 1,2,4-thiadiazolyl, pyrrolyl, pyrazolyl, oxazolyl, isoxazolyl, oxadiazolyl, benzofuranyl, benzothienyl, benzothiazolyl, indolyl, indazolyl, quinolinyl, isoquinolinyl, purinyl, carbazolyl, benzimidazolyl, pyrrolopyridyl, pyrrolopyrimidinyl, pyrazolopyridyl, pyrazolopyrimidinyl, acridinyl, phenazinyl, benzoxazolyl, benzothiadiazolyl, benzoxadiazolyl, benzotriazolyl, isoquinolinyl, indyl, isothiazolyl, pseudoindolyl, oxadiazolyl, purinyl, phthalazinyl, pteridyl, quinazolinyl, quinoxalinyl, triazinyl, and thiadiazolyl.

4. The compound according to claim 1, wherein, the alkyl is selected from a group consisting of methyl, ethyl, n-propyl, isopropyl, 2-methyl-1-propyl, 2-methyl-2-propyl, 2-methyl-1-butyl, 3-methyl-1-butyl, 2-methyl-3-butyl, 2,2-dimethyl-1-propyl, 2-methyl-1-pentyl, 3-methyl-1-pentyl, 4-methyl-1-pentyl, 2-methyl-2-pentyl, 3-methyl-2-pentyl, 4-methyl-2-pentyl, 2,2-dimethyl-1-butyl, 3,3-dimethyl-1-butyl, 2-ethyl-1-butyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, iso-pentyl, neopentyl, tert-pentyl, hexyl, heptyl, and octyl.

5. The compound according to claim 1, wherein, the compound is one of the following substances: ##STR00047##

6. A method for preparing the compound according to claim 1, comprising the following steps when M is CF.sub.3: 1) adding R.sub.1, R.sub.2, R.sub.3-trisubstituted chlorosilane, trifluoroethanol, hexamethylphosphoramide into a solvent, performing cooling to −80° C. to −60° C., and then adding dropwise lithium diisopropylamide with a syringe pump; after completion of adding dropwise, performing thorough stirring, then performing heating to room temperature, and performing stirring again until the trifluoroethanol is completely consumed; adding triethylchlorosilane at 0-4° C., carrying out a reaction under stirring, and performing separating by column chromatography to obtain a compound 4; 2) adding a fluorinating agent Select-Fluor into a mixed solvent of acetonitrile and dichloromethane, and adding the compound 4 at 0-4° C., and subsequently carrying out a reaction at room temperature for 8-12 h, quenching the reaction with water, and performing separating by column chromatography to obtain a compound 5; and 3) adding the compound 5 into methanol, followed by addition of sodium borohydride in batches, and carrying out a reaction at 0-4° C.; after completion of the reaction, adding water to quench the reaction, and performing separating by column chromatography to obtain a compound A; wherein the chemical equation is as follows: ##STR00048##

7. A method for preparing the compound according to claim 1, comprising the following steps when M is CF.sub.2H: 1) adding a compound 4 into a solvent, and adding dropwise concentrated hydrochloric acid to the resulting solution at 0-4° C.; after completion of adding dropwise, performing heating to room temperature and carrying out a reaction under stirring; after completion of the reaction, adding water to quench the reaction, and performing separating by column chromatography to obtain a compound 6; and 2) dissolving the compound 6 in a solvent, adding sodium borohydride in batches at 0-4° C., and carrying out a reaction; and after completion of the reaction, adding water to quench the reaction, and performing separating by column chromatography to obtain a compound B; wherein the chemical equation is as follows: ##STR00049##

8. An application of the compound according to claim 1, wherein the compound is used as a trifluoroethanolation reagent when M is CF.sub.3, and the compound is used as a difluoroethanolation reagent when M is CF.sub.2H.

9. The application according to claim 8, wherein, the trifluoroethanolation reagent is subjected to allylation to prepare a trifluoromethyl homoallyl alcohol compound, specifically by the steps of: carrying out a reaction between the trifluoroethanolation reagent, allyl sulfone, a catalyst and an oxidant under stirring in an organic solvent at 50-100° C. under nitrogen protection; after completion of the reaction, quenching the reaction by a tetrabutylammonium fluoride solution, and then performing separating and purifying to obtain the corresponding α-trifluoromethyl homoallyl alcohol compound with the following reaction formula: ##STR00050## wherein the R group represents a substituent group on allyl sulfone and is aryl, heteroaryl, alkyl, substituted alkyl, aroyl, alkanoyl, substituted oxyacyl, substituted aminoacyl, halogen, sulfonyl, substituted sulfuryl, alkenyl, alkynyl, cyano, nitro, amido or an aldehyde group.

10. The application according to claim 8, wherein, the trifluoroethanolation reagent and acrylamide are subjected to an alkylation reaction to prepare a trifluoromethyl alkyl alcohol compound, specifically by the steps of: carrying out a reaction between the trifluoroethanolation reagent, acrylamide, a catalyst and an oxidant under stirring in an organic solvent at 50-100° C. under nitrogen protection; after completion of the reaction, quenching the reaction by a tetrabutylammonium fluoride solution, and then performing separating and purifying to obtain the corresponding α-trifluoromethyl alkyl alcohol compound I with the following reaction formula: ##STR00051## wherein the R group represents a substituent group on the aromatic ring of acrylamide, and includes aryl, alkyl, aroyl, alkanoyl, substituted oxyacyl, halogen, cyano, nitro or alkoxy.

11. The application according to claim 8, wherein, the trifluoroethanolation reagent and cinnamic acid are subjected to an alkenylation reaction to prepare a trifluoromethyl allyl alcohol compound, specifically by the steps of: carrying out a reaction between the trifluoroethanolation reagent, cinnamic acid, a catalyst and an oxidant under stirring in an organic solvent at 50-100° C. under nitrogen protection; after completion of the reaction, quenching the reaction by a tetrabutylammonium fluoride solution, and then performing separating and purifying to obtain the corresponding α-trifluoromethyl allyl alcohol compound with the following reaction formula: ##STR00052## wherein the R group represents a substituent group on the aromatic ring of cinnamic acid, and is selected from a group consisting of aryl, alkyl, aroyl, alkanoyl, substituted oxyacyl, halogen, and alkoxy, with the substituent group being one or more, and the substituent groups being the same or different when a plurality of substituent groups are contained.

12. The application according to claim 8, wherein, the difluoroethanolation reagent and allyl sulfone are subjected to a reaction to prepare a difluoromethyl homoallyl alcohol compound, specifically by the steps of: carrying out a reaction between the difluoroethanolation reagent, allyl sulfone, a catalyst, an oxidant under stirring in an organic solvent at 50-100° C. under nitrogen protection; after completion of the reaction, quenching the reaction by a tetrabutylammonium fluoride solution, and then performing separating and purifying to obtain the α-difluoromethyl homoallyl alcohol compound.

13. The application according to claim 8, wherein, the difluoroethanolation reagent and acrylamide are subjected to a reaction to prepare a difluoromethyl alkyl alcohol compound, specifically by the steps of: carrying out a reaction between the difluoroethanolation reagent, acrylamide, a catalyst, an oxidizer under stirring in an organic solvent at 50-100° C. under nitrogen protection; after completion of the reaction, quenching the reaction by a tetrabutylammonium fluoride solution, and then performing separating and purifying to obtain the α-difluoromethyl alkyl alcohol compound.

14. The application according to claim 8, wherein, the difluoroethanolation reagent and cinnamic acid are subjected to a reaction to prepare a difluoromethyl allyl alcohol compound, specifically by the steps of: carrying out a reaction between the difluoroethanolation reagent, cinnamic acid, a catalyst and an oxidant under stirring in an organic solvent at 50-100° C. under nitrogen protection; after completion of the reaction, quenching the reaction by a tetrabutylammonium fluoride solution, and then performing separating and purifying to obtain the α-difluoromethyl alkyl alcohol compound.

Description

DETAILED DESCRIPTION OF THE EMBODIMENTS

[0059] The disclosure will be further described in detail below in conjunction with embodiments in order to enable a person skilled in the art to better understand the technical solutions of the present disclosure.

Embodiment 1

[0060] Ethyl 5,5,5-trifluoro-4-hydroxy-2-methylene pentanoate, with a synthetic route and a preparation method as follows:

##STR00014##

[0061] Under a nitrogen atmosphere, a magnetic stir bar was placed into a dry 10 mL Schlenk tube, and Mn(OAc).sub.2.4H.sub.2O (14.7 mg, 0.06 mmol, 20 mol %), 7a (152.4 mg, 0.6 mmol, 2.0 eq.), DCM (3 mL, 0.1 M), 1a (70.2 mg, 0.3 mmol) and TBPB (145.7 mg, 0.75 mmol, 2.5 eq.) were added. Subsequently, the tube was sealed, and the mixture was heated to 70° C. and stirred for 18 h. After that, TBAF was added to the stirred material in an ice-water bath of 5° C. to be stirred for 0.5 h. The reaction mixture was quenched with water (2 mL), and subjected to extraction with DCM (3×10 mL), and the organic phases were mixed and washed with brine, dried over Na.sub.2SO.sub.4, and evaporated to dryness by using a rotary evaporator. The crude product was purified by silica gel column chromatography (200×300-mesh) and eluted with PE/EA (20/1-10/1, v/v) (PE: petroleum ether, EA: ethyl acetate) to give 53 mg (yield 71%) of the target compound as a yellow oil. The product was tested, with the results as follows:

[0062] R.sub.f=0.23 (PE/EA=8/1, v/v).

[0063] NMR spectrum:

[0064] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 6.35 (s, 1H), 5.80 (s, 1H), 4.25 (q, J=7.2 Hz, 2H), 4.16-4.08 (m, 1H), 3.63 (s, 1H), 2.78-2.57 (m, 2H), 1.32 (t, J=7.2 Hz, 3H);

[0065] .sup.13C NMR (100 MHz, CDCl.sub.3) δ 168.1, 135.2, 129.8, 124.9 (q, J=280.5 Hz), 70.0 (q, J=30.7 Hz), 61.8, 33.5, 14.2;

[0066] .sup.19F NMR (375 MHz, CDCl.sub.3) δ −79.6 (d, J=6.0 Hz, 3F).

[0067] IR (ATR): 3444, 2986, 2937, 1700, 1633, 1413, 1316, 1275, 1163, 1126, 1021, 712 cm.sup.−1.

[0068] High resolution mass spectrum HRMS (ESI, m/z): a theoretically calculated value: C.sub.8H.sub.11F.sub.3NaO.sub.3.sup.+ (M+Na).sup.+: 235.0552; found: 235.0556.

[0069] The trifluoroethanolation reagent 1a used in the embodiment was prepared as follows:

[0070] 1) dimethylphenylsilyl chloride (30 mmol), trifluoroethanol (30 mmol), HMPA (6 mL) and tetrahydrofuran as a solvent were added into a dry single-neck flask with a magnetic stirrer, and the reaction flask was placed in a low-temperature tank of −78° C., and LDA (lithium diisopropylamide, 105 mmol) was added dropwise with a syringe pump. After completion of adding dropwise, stirring was kept to be performed for 4 h, the stirred material was heated to room temperature, and then stirring was performed again until trifluoroethanol was completely consumed. Triethylchlorosilane was added at 0° C., stirring was performed for 4 h, and the stirred material was separated by column chromatography to obtain a compound 4 (1,1-difluoro-2-dimethylphenylsilyl-2-triethylsiloxyethylene);

[0071] 2) a fluorinating agent Select-Fluor (2.0 eq.) and a mixed solvent of acetonitrile and dichloromethane (4:1, v/v) were added to a dry single-neck flask with a magnetic stirrer, and the single-neck flask was placed in an ice-water bath of 0° C. The compound 4 was added to the reaction, and after completion, the reaction fluid was stirred at room temperature for 12 h, and the reaction was quenched with water, followed by separation by column chromatography to obtain a compound 5 (trifluoroacetyl phenyl dimethylsilane); and

[0072] (3) the compound 5 and methanol were added to the single-neck flask, and sodium borohydride solid was added to the reaction system in three batches, and after the reaction was completed, water was added to quench the reaction, followed by separation by column chromatography to obtain the trifluoroethanolation reagent 1a.

[0073] NMR spectrum of the trifluoroethanolation reagent 1a:

[0074] .sup.1H NMR (400 MHz, CDCl3) δ 7.61 (d, J=6.1 Hz, 2H), 7.47-7.39 (m, 3H), 3.84 (q, J=11.1 Hz, 1H), 0.49 (d, J=3.1 Hz, 6H); .sup.13C NMR (100 MHz, CDCl3) δ 134.4, 134.2, 130.3, 128.2, 127.1 (q, J=278.4 Hz), 65.3 (q, J=33.1 Hz), −4.7, −5.4; .sup.19F NMR (375 MHz, CDCl3) δ −70.6 (d, J=8.9 Hz, 3F). IR (ATR): 3441, 2963, 2919, 1428, 1253, 1148, 1085, 1044, 738, 701 cm.sup.−1.

[0075] HRMS (ESI, m/z): a theoretically calculated value: C.sub.10H.sub.13F.sub.3NaO.sup.+ (M+Na).sup.+: 257.0580; found: 257.0570.

Embodiment 2

[0076] 5,5,5-trifluoro-4-hydroxy-2-methylene-1-phenylpentan-1-one, with a synthetic route and a preparation method as follows:

##STR00015##

[0077] Under a nitrogen atmosphere, a magnetic stir bar was placed into a dry 10 mL Schlenk tube and Mn(OAc).sub.3.2H.sub.2O (16.1 mg, 0.06 mmol, 20 mol %), 7b (257.4 mg, 0.9 mmol, 3.0 eq.), DCM (3 mL, 0.1 M), 1a (70.2 mg, 0.3 mmol)) and TBPB (145.7 mg, 0.75 mmol, 2.5 eq.) were added. Subsequently, the tube was sealed, and the mixture was heated to 70° C., and stirred for 14 h. After that, TBAF was added to the stirred material in an ice-water bath of 5° C. to be stirred for 0.5 h. The reaction mixture was quenched with water (2 mL), and subjected to extraction with DCM (3×10 mL), and the organic phases were mixed and washed with brine, dried over Na.sub.2SO.sub.4, and evaporated to dryness by using a rotary evaporator. The crude product was purified by silica gel column chromatography (200×300-mesh) and eluted with PE/EA (20/1-10/1, v/v) to give 53 mg (yield 71%) of the target compound as a yellow oil. The product was tested, with the results as follows:

[0078] R.sub.f=0.40 (PE/EA=5/1, v/v).

[0079] NMR spectrum:

[0080] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.77 (d, J=7.3 Hz, 2H), 7.60 (t, J=7.3 Hz, 1H), 7.47 (t, J=7.6 Hz, 2H), 6.16 (s, 1H), 5.90 (s, 1H), 4.32 (d, J=5.2 Hz, 1H), 4.15-4.14 (m, 1H), 2.90-2.71 (m, 2H);

[0081] .sup.13C NMR (100 MHz, CDCl.sub.3) δ 199.5, 142.2, 136.7, 133.2, 131.9, 130.1, 128.5, 125.0 (q, J=280.6 Hz), 70.5 (q, J=31.2 Hz), 33.8; 19F NMR (375 MHz, CDCl.sub.3) δ −79.3 (d, J=6.0 Hz, 3F).

[0082] IR (ATR): 3418, 3064, 2933, 1648, 1446, 1338, 1275, 1223, 1163, 1036, 753 cm.sup.−1.

[0083] HRMS (ESI, m/z): a theoretically calculated value: C.sub.12H.sub.12F.sub.3O.sub.2.sup.+ (M+H).sup.+: 245.0784; found: 245.0778.

Embodiment 3

1-([[1,1′-biphenyl]-4-yl)-5,5,5-trifluoro-4-hydroxy-2-methylenepentyl-1-one

[0084] ##STR00016##

[0085] Under a nitrogen atmosphere, a magnetic stir bar was placed into a dry 10 mL Schlenk tube and Mn(OAc).sub.3.2H.sub.2O (16.1 mg, 0.06 mmol, 20 mol %), 7c (326.2 mg, 0.9 mmol, 3.0 eq.), DCM (3 mL, 0.1 M), 1a (70.2 mg, 0.3 mmol) and TBPB (145.7 mg, 0.75 mmol, 2.5 eq.) were added. Subsequently, the tube was sealed, and the mixture was heated to 70° C. and stirred for 14 h. After that, TBAF was added to the stirred material in an ice-water bath of 5° C. to be stirred for 0.5 h. The reaction mixture was quenched with water (2 mL), and subjected to extraction with DCM (3×10 mL), and the organic phases were mixed and washed with brine, dried over Na.sub.2SO.sub.4, and evaporated to dryness by using a rotary evaporator. The crude product was purified by silica gel column chromatography (200×300-mesh) and eluted with PE/EA (20/1-10/1, v/v) to give 74.9 mg (yield 78%) of the target compound as a white solid. The product was tested, with the results as follows:

[0086] R.sub.f=0.50 (PE/EA=5/1, v/v), and a boiling point (mp): 69-71° C.

[0087] NMR spectrum:

[0088] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.88 (d, J=8.3 Hz, 2H), 7.69 (d, J=8.3 Hz, 2H), 7.63 (d, J=7.3 Hz, 2H), 7.49 (t, J=7.3 Hz, 2H), 7.42 (t, J=7.2 Hz, 1H), 6.18 (s, 1H), 5.95 (s, 1H), 4.38 (d, J=4.9 Hz, 1H), 4.18-4.17 (m, 1H), 2.92-2.74 (m, 2H);

[0089] .sup.13C NMR (100 MHz, CDCl.sub.3) δ 199.1, 146.1, 142.3, 139.8, 135.3, 131.5, 130.8, 129.1, 128.5, 127.4, 127.2, 125.0 (q, J=280.8 Hz), 70.6 (q, J=30.7 Hz), 33.9;

[0090] .sup.19F NMR (375 MHz, CDCl.sub.3) δ −79.3 (d, J=6.0 Hz, 3F).

[0091] IR (ATR): 3392, 3060, 2926, 1640, 1599, 1409, 1344, 1275, 1163, 1129, 1029, 757 cm.sup.−1.

[0092] HRMS (ESI, m/z): a theoretically calculated value: C.sub.18H.sub.16F.sub.3O.sub.2.sup.+ (M+H).sup.+: 321.1097; found: 321.1096.

Embodiment 4

1-(4-chlorophenyl)-5,5,5-trifluoro-4-hydroxy-2-methylenepentyl-1-one

[0093] ##STR00017##

[0094] Under a nitrogen atmosphere, a magnetic stir bar was placed into a dry 10 mL Schlenk tube and Mn(OAc).sub.3.2H.sub.2O (16.1 mg, 0.06 mmol, 20 mol %), 7e (288.0 mg, 0.9 mmol, 3.0 eq.), DCM (3 mL, 0.1 M), 1a (70.2 mg, 0.3 mmol) and TBPB (145.7 mg, 0.75 mmol, 2.5 eq.) were added. Subsequently, the tube was sealed, and the mixture was heated to 70° C. and stirred for 14 h. After that, TBAF was added to the stirred material in an ice-water bath of 5° C. to be stirred for 0.5 h. The reaction mixture was quenched with water (2 mL), and subjected to extraction with DCM (3×10 mL), and the organic phases were mixed and washed with brine, dried over Na.sub.2SO.sub.4, and evaporated to dryness by using a rotary evaporator. The crude product was purified by silica gel column chromatography (200×300-mesh) and eluted with PE/EA (20/1-10/1, v/v) to give 57.2 mg (yield 69%) of the target compound as a yellow oil. The product was tested, with the results as follows:

[0095] R.sub.f=0.40 (PE/EA=5/1, v/v).

[0096] NMR spectrum:

[0097] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.73 (d, J=8.6 Hz, 2H), 7.45 (d, J=8.3 Hz, 2H), 6.16 (s, 1H), 5.87 (s, 1H), 4.15 (s, 1H), 3.96 (s, 1H), 2.90 2.71 (m, 2H);

[0098] .sup.13C NMR (100 MHz, CDCl.sub.3) δ 198.1, 142.1, 139.7, 135.0, 131.7, 131.4, 128.9, 124.9 (q, J=281.8 Hz), 70.4 (q, J=30.7 Hz), 33.8; .sup.19F NMR (375 MHz, CDCl.sub.3) δ −79.4 (d, J=8.9 Hz, 3F).

[0099] IR (ATR): 3437, 2930, 1651, 1588, 1478, 1402, 1334, 1275, 1163, 1129, 1092, 790 cm.sup.−1.

[0100] HRMS (ESI, m/z): a theoretically calculated value: C.sub.12H.sub.11ClF.sub.3O.sub.2.sup.+ (M+H).sup.+: 279.0394; found: 279.0389.

Embodiment 5

1-(3-chlorophenyl)-5,5,5-trifluoro-4-hydroxy-2-methylenepentyl-1-one

[0101] ##STR00018##

[0102] Under a nitrogen atmosphere, a magnetic stir bar was placed into a dry 10 mL Schlenk tube and Mn(OAc).sub.3.2H.sub.2O (16.1 mg, 0.06 mmol, 20 mol %), 7f (288.0 mg, 0.9 mmol, 3.0 eq.), DCM (3 mL, 0.1 M), 1a (70.2 mg, 0.3 mmol) and TBPB (145.7 mg, 0.75 mmol, 2.5 eq.) were added. Subsequently, the tube was sealed, and the mixture was heated to 70° C. and stirred for 14 h. After that, TBAF was added to the stirred material in an ice-water bath of 5° C. to be stirred for 0.5 h. The reaction mixture was quenched with water (2 mL), and subjected to extraction with DCM (3×10 mL), and the organic phases were mixed and washed with brine, dried over Na.sub.2SO.sub.4, and evaporated to dryness by using a rotary evaporator. The crude product was purified by silica gel column chromatography (200×300-mesh) and eluted with PE/EA (20/1-10/1, v/v) to give 65.1 mg (yield 78%) of the target compound as a yellow oil. The product was tested, with the results as follows:

[0103] R.sub.f=0.40 (PE/EA=5/1, v/v).

[0104] NMR spectrum:

[0105] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.73 (s, 1H), 7.63 (d, J=8.0 Hz, 1H), 7.56 (d, J=8.0 Hz, 1H), 7.41 (t, J=7.8 Hz, 1H), 6.19 (s, 1H), 5.90 (s, 1H), 4.19 4.13 (m, 1H), 3.85 (d, J=5.8 Hz, 1H), 2.91-2.71 (m, 2H);

[0106] .sup.13C NMR (100 MHz, CDCl.sub.3) δ 197.9, 142.0, 138.5, 134.8, 133.0, 132.3, 129.9, 129.9, 128.0, 124.9 (q, J=280.8 Hz), 70.2 (q, J=30.9 Hz), 33.6;

[0107] .sup.19F NMR (375 MHz, CDCl.sub.3) δ −79.4 (d, J=6.0 Hz, 3F). IR (ATR): 3418, 3071, 2930, 1651, 1420, 1334, 1275, 1163, 1129, 1033, 768 cm.sup.−1.

[0108] HRMS (ESI, m/z): a theoretically calculated value: C.sub.12H.sub.10ClF.sub.3NaO.sub.2.sup.+ (M+Na).sup.+: 301.0214; found: 301.0216.

Embodiment 6

1-(4-bromophenyl)-5,5,5-trifluoro-4-hydroxy-2-methylenepentyl-1-one

[0109] ##STR00019##

[0110] Under a nitrogen atmosphere, a magnetic stir bar was placed into a dry 10 mL Schlenk tube and Mn(OAc).sub.3.2H.sub.2O (16.1 mg, 0.06 mmol, 20 mol %), 7h (329.0 mg, 0.9 mmol, 3.0 eq.), DCM (3 mL 0.1 M), 1a (70.2 mg, 0.3 mmol) and TBPB (145.7 mg, 0.75 mmol, 2.5 eq.) were added. Subsequently, the tube was sealed, and the mixture was heated to 70° C. and stirred for 14 h. After that, TBAF was added to the stirred material in an ice-water bath of 5° C. to be stirred for 0.5 h. The reaction mixture was quenched with water (2 mL), and subjected to extraction with DCM (3×10 mL), and the organic phases were mixed and washed with brine, dried over Na.sub.2SO.sub.4, and evaporated to dryness by using a rotary evaporator. The crude product was purified by silica gel column chromatography (200×300-mesh) and eluted with PE/EA (20/1-10/1, v/v) to give 78.9 mg (yield 81%) of the target compound as a yellow oil. The product was tested, with the results as follows:

[0111] R.sub.f=0.50 (PE/EA=5/1, v/v).

[0112] NMR spectrum:

[0113] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.66-7.60 (m, 4H), 6.17 (s, 1H), 5.87 (s, 1H), 4.15 4.14 (m, 1H), 3.92-3.91 (m, 1H), 2.90-2.71 (m, 2H);

[0114] .sup.13C NMR (100 MHz, CDCl.sub.3) δ 198.3, 142.1, 135.5, 131.9, 131.8, 131.5, 128.4, 124.9 (q, J=280.8 Hz), 70.4 (q, J=30.9 Hz), 33.7;

[0115] .sup.19F NMR (375 MHz, CDCl.sub.3) δ −79.4 (d, J=6.0 Hz, 3F).

[0116] IR (ATR): 3422, 2920, 2855, 1648, 1584, 1398, 1275, 1167, 1133, 1074, 790 cm.sup.−1.

[0117] HRMS (ESI, m/z): a theoretically calculated value: C.sub.12H.sub.11BrF.sub.3O.sub.2.sup.+ (M+H).sup.+: 322.9889; found: 322.9888.

Embodiment 7

5,5,5-trifluoro-4-hydroxy-1-(4-iodophenyl)-2-methylenepentyl-1-one

[0118] ##STR00020##

[0119] Under a nitrogen atmosphere, a magnetic stir bar was placed into a dry 10 mL Schlenk tube and Mn(OAc).sub.3.2H.sub.2O (16.1 mg, 0.06 mmol, 20 mol %), 7i (370.8 mg, 0.9 mmol, 3.0 eq.), DCM (3 mL, 0.1 M), 1a (70.2 mg, 0.3 mmol)) and TBPB (145.7 mg, 0.75 mmol, 2.5 eq.) were added. Subsequently, the tube was sealed, and the mixture was heated to 70° C. and stirred for 14 h. After that, the Schlenk tube was placed in an ice-water bath of 5° C., and TBAF was added to be stirred for 0.5 h. The reaction mixture was then quenched with water (2 mL) and subjected to extraction with DCM (3×10 mL), and the organic phases were mixed and washed with brine, dried over Na.sub.2SO.sub.4 and evaporated to dryness by using a rotary evaporator. The crude product was purified by silica gel column chromatography (200×300-mesh) and eluted with PE/EA (20/1-10/1, v/v) to give 72.0 mg (yield 65%) of the target compound as a colorless oil. The product was tested, with the results as follows:

[0120] R.sub.f=0.50 (PE/EA=5/1, v/v).

[0121] NMR spectrum:

[0122] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.83 (d, J=8.3 Hz, 2H), 7.48 (d, J=8.3 Hz, 2H), 6.16 (s, 1H), 5.86 (s, 1H), 4.14 (s, 1H), 3.95 (d, J=4.6 Hz, 1H), 2.89 2.70 (m, 2H);

[0123] .sup.13C NMR (100 MHz, CDCl.sub.3) δ 198.5, 142.1, 137.9, 136.0, 131.8, 131.4, 124.9 (q, J=280.8 Hz), 101.0, 70.3 (q, J=31.1 Hz), 33.8;

[0124] .sup.19F NMR (375 MHz, CDCl.sub.3) δ −79.4 (d, J=6.0 Hz, 3F).

[0125] IR (ATR): 3429, 2926, 2855, 1648, 1480, 1390, 1275, 1163, 1126, 1100, 787 cm.sup.−1.

[0126] HRMS (ESI, m/z): a theoretically calculated value: C.sub.12H.sub.10F.sub.3INaO.sub.2.sup.+ (M+Na).sup.+: 392.9570; found: 392.9560.

Embodiment 8

5,5,5-trifluoro-4-hydroxy-2-methylene pentanoic acid-4-bromo-2-ene-butyl Ester

[0127] ##STR00021##

[0128] Under a nitrogen atmosphere, a magnetic stir bar was placed into a dry 10 mL Schlenk tube and Mn(OAc).sub.3.2H.sub.2O (16.1 mg, 0.06 mmol, 20 mol %), 7j (323.1 mg, 0.9 mmol, 3.0 eq.), DCM (3 mL, 0.1 M), 1a (70.2 mg, 0.3 mmol) and TBPB (145.7 mg, 0.75 mmol, 2.5 eq.) were added. Subsequently, the tube was sealed, and the mixture was heated to 70° C. and stirred for 14 h. After that, the Schlenk tube was placed in an ice-water bath of 5° C., and TBAF was added to be stirred for 0.5 h. The reaction mixture was quenched with water (2 mL) and subjected to extraction with DCM (3×10 mL), and the organic phases were mixed and washed with brine, dried over Na.sub.2SO.sub.4, and evaporated to dryness by using a rotary evaporator. The crude product was purified by silica gel column chromatography (200×300-mesh) and eluted with PE/EA (20/1-10/1, v/v) to give 45.7 mg (yield 48%) of the target compound as a colorless oil. The product was tested, with the results as follows:

[0129] R.sub.f=0.57 (PE/EA=4/1 v/v).

[0130] NMR spectrum:

[0131] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 6.39 (s, 1H), 5.95-5.92 (m, 2H), 5.85 (s, 1H), 4.71 (d, J=4.3 Hz, 2H), 4.18-4.07 (m, 3H), 3.28 (s, 1H), 2.80-2.58 (m, 2H);

[0132] .sup.13C NMR (100 MHz, CDCl.sub.3) δ 167.5, 134.9, 130.4, 130.3, 127.9, 124.9 (q, J=281.2 Hz), 69.9 (q, J=31.2 Hz), 64.7, 43.9, 33.5.

[0133] .sup.19F NMR (375 MHz, CDCl.sub.3) δ −79.6 (d, J=8.9 Hz, 3F).

[0134] IR (ATR): 3429, 2922, 2855, 2359, 2259, 1715, 1126, 783 cm.sup.−1.

[0135] HRMS (ESI, m/z): a theoretically calculated value: C.sub.10H.sub.12F.sub.3O.sub.3.sup.+ (M-Br).sup.+: 237.0733; found: 237.0726.

Embodiment 9

5,5,5-trifluoro-1-(furan-2-yl)-4-hydroxy-2-methylenepentyl-1-one

[0136] ##STR00022##

[0137] Under a nitrogen atmosphere, a magnetic stir bar was placed into a dry 10 mL Schlenk tube and Mn(OAc).sub.3.2H.sub.2O (16.1 mg, 0.06 mmol, 20 mol %), 7n (248.7 mg, 0.9 mmol, 3.0 eq.), DCM (3 mL, 0.1 M), 1a (70.2 mg, 0.3 mmol) and TBPB (145.7 mg, 0.75 mmol, 2.5 eq.) were added. Subsequently, the tube was sealed, and the mixture was heated to 70° C. and stirred for 14 h. After that, the Schlenk tube was placed in an ice-water bath of 5° C., and TBAF was added to be stirred for 0.5 h. The reaction mixture was quenched with water (2 mL) and subjected to extraction with DCM (3×10 mL), and the organic phases were mixed and washed with brine, dried over Na.sub.2SO.sub.4, and evaporated to dryness by using a rotary evaporator. The crude product was purified by silica gel column chromatography (200×300-mesh) and eluted with PE/EA (20/1-10/1, v/v) to give 56.0 mg (yield 80%) of the target compound as a yellow oil. The product was tested, with the results as follows:

[0138] R.sub.f=0.40 (PE/EA=5/1, v/v).

[0139] NMR spectrum:

[0140] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.71-7.70 (m, 1H), 7.26-7.25 (m, 1H), 6.59-6.58 (m, 1H), 6.27 (s, 1H), 6.07 (s, 1H), 4.15-4.07 (m, 1H), 2.83-2.65 (m, 2H);

[0141] .sup.13C NMR (100 MHz, CDCl.sub.3) δ 184.7, 151.4, 148.3, 141.8, 130.0, 124.9 (q, J=280.8 Hz), 121.9, 112.6, 70.5 (q, J=31.2 Hz), 34.0;

[0142] .sup.19F NMR (375 MHz, CDCl.sub.3) δ −79.4 (d, J=6.0 Hz, 3F).

[0143] IR (ATR): 3407, 3142, 2933, 1618, 1465, 1394, 1275, 1163, 1129, 1029, 768 cm.sup.−1.

[0144] HRMS (ESI, m/z): a theoretically calculated value: C.sub.10H.sub.10F.sub.3O.sub.3.sup.+ (M+H).sup.+: 235.0577; found: 235.0575.

Embodiment 10

N,N-diphenyl 5,5,5-trifluoro-4-hydroxy-2-methylene Pentanamide

[0145] ##STR00023##

[0146] Under a nitrogen atmosphere, a magnetic stir bar was placed into a dry 10 mL Schlenk tube and Mn(OAc).sub.2.4H.sub.2O (14.7 mg, 0.06 mmol, 20 mol %), 7z (339.3 mg, 0.9 mmol, 3.0 eq.), DCM (3 mL, 0.1 M), 1a (70.2 mg, 0.3 mmol) and TBPB (145.7 mg, 0.75 mmol, 2.5 eq.) were added. Subsequently, the tube was sealed, and the mixture was heated to 70° C. and stirred for 14 h. After that, the Schlenk tube was placed in an ice-water bath of 5° C., and TBAF was added to be stirred for 0.5 h. The reaction mixture was quenched with water (2 mL) and subjected to extraction with DCM (3×10 mL), and the organic phases were mixed and washed with brine, dried over Na.sub.2SO.sub.4, and evaporated to dryness by using a rotary evaporator. The crude product was purified by silica gel column chromatography (200×300-mesh) and eluted with PE/EA (8/1, v/v) to give 54 mg (yield 54%) of the target compound as a colorless oil. The product was tested, with the results as follows:

[0147] R.sub.f=0.27 (PE/EA=4/1, v/v).

[0148] NMR spectrum:

[0149] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.37 (t, J=7.8 Hz, 4H), 7.29-7.25 (m, 2H), 7.19-7.17 (m, 4H), 5.45 (s, 1H), 5.32 (s, 1H), 4.15-4.07 (m, 1H), 2.64-2.50 (m, 2H);

[0150] .sup.13C NMR (100 MHz, CDCl.sub.3) δ 172.4, 143.2, 138.6, 129.5, 127.3, 127.2, 125.8, 125.0 (q, J=280.3 Hz), 71.1 (q, J=30.7 Hz), 34.8; .sup.19F NMR (375 MHz, CDCl.sub.3) δ −79.5 (d, J=6.0 Hz, 3F).

[0151] IR (ATR): 3288, 2963, 2930, 1644, 1592, 1491, 1364, 1275, 1163, 1126, 1029, 693 cm.sup.−1.

[0152] HRMS (ESI, m/z): a theoretically calculated value: C.sub.18H.sub.17F.sub.3NO.sub.2.sup.+ (M+H).sup.+: 336.1206; found: 336.1197.

Embodiment 11

4-(5,5,5-trifluoro-4-hydroxy-2-methylene valeryl)benzonitrile

[0153] ##STR00024##

[0154] Under a nitrogen atmosphere, a magnetic stir bar was placed into a dry 10 mL Schlenk tube and Mn(OAc).sub.3.2H.sub.2O (16.1 mg, 0.06 mmol, 20 mol %), 7m (280.2 mg, 0.9 mmol, 3.0 eq.), DCM (3 mL, 0.1 M), 1a (70.2 mg, 0.3 mmol) and TBPB (145.7 mg, 0.75 mmol, 2.5 eq.) were added. Subsequently, the tube was sealed, and the mixture was heated to 70° C. and stirred for 14 h. After that, the Schlenk tube was placed in an ice-water bath of 5° C., and TBAF was added to be stirred for 0.5 h. The reaction mixture was quenched with water (2 mL) and subjected to extraction with DCM (3×10 mL), and the organic phases were mixed and washed with brine, dried over Na.sub.2SO.sub.4, and evaporated to dryness by using a rotary evaporator. The crude product was purified by silica gel column chromatography (200×300-mesh) and eluted with PE/EA (20/1-10/1, v/v) to give 65.0 mg (yield 80%) of the target compound as a yellow oil. The product was tested, with the results as follows:

[0155] R.sub.f=0.30 (PE/EA=5/1, v/v).

[0156] NMR spectrum:

[0157] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.83 (d, J=8.6 Hz, 2H), 7.77 (d, J=8.6 Hz, 2H), 6.24 (s, 1H), 5.86 (s, 1H), 4.23-4.15 (m, 1H), 3.42 (s, 1H), 2.95-2.74 (m, 2H);

[0158] .sup.13C NMR (100 MHz, CDCl.sub.3) δ 197.4, 142.0, 140.7, 132.9, 132.4, 130.2, 124.9 (q, J=280.3 Hz), 118.0, 116.1, 69.9 (q, J=30.9 Hz), 33.3;

[0159] .sup.19F NMR (375 MHz, CDCl.sub.3) δ −79.4 (d, J=6.0 Hz, 3F).

[0160] IR (ATR): 3448, 2922, 2851, 2233, 1655, 1402, 1275, 1163, 1129, 1029, 798 cm.sup.−1.

[0161] HRMS (ESI, m/z): a theoretically calculated value: C.sub.13H.sub.10F.sub.3NNaO.sub.2.sup.+ (M+Na).sup.+: 292.0556; found: 292.0567.

Embodiment 12

4-ene-4-phenyl-1,1,1-trifluoropentan-2-ol

[0162] ##STR00025##

[0163] Under a nitrogen atmosphere, a magnetic stir bar was placed into a dry 10 mL Schlenk tube and Mn(OAc).sub.2.4H.sub.2O (29.4 mg, 0.12 mmol, 20 mol %), 7ac (465.0 mg, 1.8 mmol, 3.0 eq.), DCM (6 mL, 0.1 M), 1a (140.4 mg, 0.6 mmol) and TBPB (291.3 mg, 1.5 mmol, 2.5 eq) were added. Subsequently, the tube was sealed, and the mixture was heated to 70° C. and stirred for 18 h. After that, the Schlenk tube was placed in an ice-water bath of 5° C., and TBAF was added to be stirred for 0.5 h. The reaction mixture was quenched with water (2 mL) and subjected to extraction with DCM (3×10 mL). The organic phases were mixed and washed with brine, dried over Na.sub.2SO.sub.4, and evaporated to dryness by using a rotary evaporator. The crude product was purified by silica gel column chromatography (200×300-mesh) and eluted with PE/EA (30/1-20/1, v/v) to give 56 mg (yield 43%) of the target compound as a yellow oil. The product was tested, with the results as follows:

[0164] R.sub.f=0.47 (PE/EA=8/1, v/v).

[0165] NMR spectrum:

[0166] .sup.1H-NMR (400 MHz, CDCl.sub.3) δ 7.42-7.31 (m, 5H), 5.49 (s, 1H), 5.28 (s, 1H), 4.00 (bs, 1H), 3.11-2.67 (m, 2H), 2.21 (s, 1H);

[0167] .sup.13C-NMR (100 MHz, CDCl.sub.3) δ 142.7, 139.4, 128.8, 128.3, 126.3, 125.2 (q, J=279.8 Hz), 121.1, 117.0, 68.7 (q, J=30.9 Hz), 36.3;

[0168] .sup.19F-NMR (375 MHz, CDCl.sub.3) δ −79.5 (d, J=6.0 Hz, 3F).

[0169] IR (ATR): 3422, 3086, 3030, 2960, 2930, 1633, 1446, 1390, 1029, 701 cm.sup.−1.

[0170] HRMS (ESI, m/z): a theoretically calculated value: C.sub.11H.sub.12F.sub.3O.sup.+ (M+H).sup.+: 217.0835; found: 217.0828.

Embodiment 13

[0171] Epiandrosterone Derivative

##STR00026##

[0172] Under a nitrogen atmosphere, a magnetic stir bar was placed into a dry 10 mL Schlenk tube and added Mn(OAc).sub.2.4H.sub.2O (14.7 mg, 0.06 mmol, 20 mol %), 7aj (298.8 mg, 0.6 mmol, 2.0 eq.), DCM (3 mL, 0.1 M), 1a (70.2 mg, 0.3 mmol) and TBPB (145.7 mg, 0.75 mmol, 2.5 eq.) were added. Subsequently, the tube was sealed, and the mixture was heated to 70° C. and stirred for 18 h. After that, the Schlenk tube was placed in an ice-water bath of 5° C., and TBAF was added to be stirred for 0.5 h. The reaction mixture was quenched with water (2 mL) and subjected to extraction with DCM (3×10 mL). The organic phases were mixed and washed with brine, dried over Na.sub.2SO.sub.4, and evaporated to dryness by using a rotary evaporator. The crude product was purified by silica gel column chromatography (200×300-mesh) and eluted with PE/EA (5/1, v/v) to give 81 mg (yield 59%) of the target compound as a white solid. The product was tested, with the results as follows:

[0173] R.sub.f=0.24 (PE/EA=2/1, v/v). mp: 95-97° C.

[0174] NMR spectrum:

[0175] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 6.31 (s, 1H), 5.77 (s, 1H), 4.81-4.73 (m, 1H), 4.11-4.08 (m, 1H), 3.82 (s, 1H), 2.76-2.55 (m, 2H), 2.46-2.39 (m, 1H), 2.11-2.01 (m, 1H), 1.95-1.75 (m, 5H), 1.67-1.19 (m, 12H), 1.09-0.96 (m, 2H), 0.86 (s, 3H), 0.85 (s, 3H), 0.75-0.69 (m, 1H);

[0176] .sup.13C NMR (100 MHz, CDCl.sub.3) δ 221.7, 167.5, 135.5, 129.5, 124.9 (q, J=280.8 Hz), 75.1, 70.0 (q, J=30.9 Hz), 54.3, 51.4, 47.9, 44.7, 36.7, 36.0, 35.7, 35.1, 33.9, 33.5, 31.6, 30.9, 28.3, 27.4, 21.9, 20.6, 13.9, 12.3;

[0177] .sup.19F NMR (375 MHz, CDCl.sub.3) δ −79.5-−79.5 (m, 3F, 3F′).

[0178] IR (ATR): 3370, 2933, 2855, 1718, 1633, 1405, 1312, 1291, 1178, 1122, 1014, 716 cm.sup.−1.

[0179] HRMS (ESI, m/z): a theoretically calculated value: C.sub.25H.sub.35F.sub.3NaO.sub.4.sup.+ (M+Na).sup.+: 479.2380; found: 479.2370.

Embodiment 14

5,5,5-trifluoro-4-hydroxy-2-methylene Pentanoic Acid-indan-1-yl Ester

[0180] ##STR00027##

[0181] Under a nitrogen atmosphere, a magnetic stir bar was placed into a dry 10 mL Schlenk tube and Mn(OAc).sub.2.4H.sub.2O (14.7 mg, 0.06 mmol, 20 mol %), 7a (152.4 mg, 0.6 mmol, 2.0 eq.), DCM (3 mL, 0.1 M), 1a (70.2 mg, 0.3 mmol) and TBPB (145.7 mg, 0.75 mmol, 2.5 eq.) were added. Subsequently, the tube was sealed, and the mixture was heated to 70° C. and stirred for 18 h. After that, the Schlenk tube was placed in an ice-water bath of 5° C., and TBAF was added to be stirred for 0.5 h. The reaction mixture was quenched with water (2 mL) and subjected to extraction with DCM (3×10 mL). The organic phases were mixed and washed with brine, dried over Na.sub.2SO.sub.4, and evaporated to dryness by using a rotary evaporator. The crude product was purified by silica gel column chromatography (200×300-mesh) and eluted with PE/EA (20/1-10/1, v/v) to give 66 mg (yield 73%) of the target compound as a colorless oil. The product was tested, with the results as follows:

[0182] R.sub.f=0.30 (PE/EA=8/1, v/v).

[0183] NMR spectrum:

[0184] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.43 (d, J=7.3 Hz, 1H), 7.35-7.31 (m, 2H), 7.25 (t, J=6.3 Hz, 1H), 6.32-6.28 (m, 2H), 5.79 (s, 1H), 4.14-4.12 (m, 1H), 3.67 (s, 1H), 3.18 3.11 (m, 1H), 2.96-2.89 (m, 1H), 2.80-2.76 (m, 1H), 2.66-2.52 (m, 2H), 2.20-2.13 (m, 1H);

[0185] .sup.13C NMR (100 MHz, CDCl.sub.3) δ 168.1, 144.6, 140.6, 135.3, 130.1, 130.0 (C′), 129.4, 127.0, 125.8, 125.7 (C′), 125.0, 124.9 (q, J=280.8 Hz), 79.9, 71.2 (q, J=30.9 Hz, C), 70.1 (q, J=31.2 Hz, C′), 33.6, 32.4, 30.3;

[0186] .sup.19F NMR (375 MHz, CDCl.sub.3) δ −79.5-−79.5 (m, 3F, 3F′).

[0187] IR (ATR): 3425, 2941, 2855, 1703, 1633, 1435, 1320, 1275, 1170, 1126, 1014, 708 cm.sup.−1.

[0188] HRMS (ESI, m/z): a theoretically calculated value: C.sub.15H.sub.15F.sub.3NaO.sub.3.sup.+ (M+Na).sup.+: 323.0866; found: 323.0867.

Embodiment 15

5,5,5-trifluoro-4-hydroxy-2-methylenepentanoic Acid benzo[d][1,3]dioxolan-5-yl Methyl Ester

[0189] ##STR00028##

[0190] Under a nitrogen atmosphere, a magnetic stir bar was placed into a dry 10 mL Schlenk tube and Mn(OAc).sub.2.4H.sub.2O (14.7 mg, 0.06 mmol, 20 mol %), 7t (216 mg, 0.6 mmol, 2.0 eq.), DCM (3 mL, 0.1 M), 1a (70.2 mg, 0.3 mmol) and TBPB (145.7 mg, 0.75 mmol, 2.5 eq.) were added. Subsequently, the tube was sealed, and the mixture was heated to 70° C. and stirred for 18 h. After that, the Schlenk tube was placed in an ice-water bath of 5° C., and TBAF was added to be stirred for 0.5 h. The reaction mixture was quenched with water (2 mL), and subjected to extraction with DCM (3×10 mL). The organic phases were mixed and washed with brine, dried over Na.sub.2SO.sub.4, and evaporated to dryness by using a rotary evaporator. The crude product was purified by silica gel column chromatography (200×300-mesh) and eluted with PE/EA (8/1, v/v) to give 61 mg (yield 64%) of the target compound as a colorless oil. The product was tested, with the results as follows:

[0191] R.sub.f=0.33 (PE/EA=4/1, v/v).

[0192] NMR spectrum:

[0193] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 6.85-6.77 (m, 3H), 6.35 (s, 1H), 5.96 (s, 2H), 5.81 (s, 1H), 5.11 (s, 2H), 4.15-4.07 (m, 1H), 3.10 (s, 1H), 2.78-2.56 (m, 2H);

[0194] .sup.13C NMR (100 MHz, CDCl.sub.3) δ 167.7, 148.0, 147.8, 135.0, 130.2, 129.2, 124.9 (q, J=280.0 Hz), 122.5, 109.1, 108.4, 101.4, 69.9 (q, J=31.1 Hz), 67.4, 33.5;

[0195] .sup.19F NMR (375 MHz, CDCl.sub.3) δ −79.6 (d, J=6.0 Hz, 3F).

[0196] IR (ATR): 3422, 2900, 1707, 1633, 1491, 1446, 1327, 1252, 1167, 1122, 1036, 712 cm.sup.−1.

[0197] HRMS (ESI, m/z): a theoretically calculated value: C.sub.14H.sub.13F.sub.3NaO.sub.5.sup.+ (M+Na).sup.+: 341.0607; found: 341.0594.

Embodiment 16

5,5,5-trifluoro-4-hydroxy-2-methylenepentanoic acid-4-bromobenzyl Ester

[0198] ##STR00029##

[0199] Under a nitrogen atmosphere, a magnetic stir bar was placed into a dry 10 mL Schlenk tube and Mn(OAc).sub.2.4H.sub.2O (14.7 mg, 0.06 mmol, 20 mol %), 7v (355.5 mg, 0.9 mmol, 3.0 eq.), DCM (3 mL, 0.1 M), 1a (70.2 mg, 0.3 mmol) and TBPB (145.7 mg, 0.75 mmol, 2.5 eq.) were added. Subsequently, the tube was sealed, and the mixture was heated to 70° C. and stirred for 18 h. After that, the Schlenk tube was placed in an ice-water bath of 5° C., and TBAF was added to be stirred for 0.5 h. The reaction mixture was quenched with water (2 mL) and subjected to extraction with DCM (3×10 mL). The organic phases were mixed and washed with brine, dried over Na.sub.2SO.sub.4 and evaporated to dryness by using a rotary evaporator. The crude product was purified by silica gel column chromatography (200×300-mesh) and eluted with PE/EA (20/1-10/1, v/v) to give 60 mg (yield 56%) of the target compound as a yellow oil. The product was tested, with the results as follows:

[0200] R.sub.f=0.23 (PE/EA=4/1, v/v).

[0201] NMR spectrum:

[0202] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.51 (d, J=8.3 Hz, 2H), 7.25 (d, J=8.4 Hz, 2H), 6.39 (s, 1H), 5.85 (s, 1H), 5.17 (s, 2H), 4.17-4.09 (m, 1H), 2.81-2.59 (m, 3H);

[0203] .sup.13C NMR (100 MHz, CDCl.sub.3) δ 167.6, 134.8, 134.5, 132.0, 130.4, 130.1, 124.9 (q, J=279.8 Hz), 122.7, 69.9 (q, J=31.1 Hz), 66.6, 33.4;

[0204] .sup.19F NMR (375 MHz, CDCl.sub.3) δ −79.6 (d, J=6.0 Hz, 3F).

[0205] IR (ATR): 3422, 3528, 2498, 1715, 1633, 1439, 1331, 1275, 1170, 1126, 1014, 712 cm.sup.−1.

[0206] HRMS (ESI, m/z): a theoretically calculated value: C.sub.13H.sub.12BrF.sub.3NaO.sub.3.sup.+ (M+Na).sup.+: 374.9814; found: 374.9807.

Embodiment 17

5,5,5-trifluoro-4-hydroxy-2-methylenepentanoic acid-naphthalene-2-methyl Ester

[0207] ##STR00030##

[0208] Under a nitrogen atmosphere, a magnetic stir bar was placed into a dry 10 mL Schlenk tube and Mn(OAc).sub.2.4H.sub.2O (14.7 mg, 0.06 mmol, 20 mol %), 7w (329.8 mg, 0.9 mmol, 3.0 eq.), DCM (3 mL, 0.1 M), 1a (70.2 mg, 0.3 mmol) and TBPB (145.7 mg, 0.75 mmol, 2.5 eq.) were added. Subsequently, the tube was sealed, and the mixture was heated to 70° C. and stirred for 18 h. After that, TBAF was added to the stirred material in an ice-water bath of 5° C. to be stirred for 0.5 h. The reaction mixture was quenched with water (2 mL) and subjected to extraction with DCM (3×10 mL). The organic phases were mixed and washed with brine, dried over Na.sub.2SO.sub.4, and evaporated to dryness by using a rotary evaporator. The crude product was purified by silica gel column chromatography (200×300-mesh) and eluted with PE/EA (20/1-10/1, v/v) to give 70 mg (yield 72%) of the target compound as a colorless oil. The product was tested, with the results as follows:

[0209] R.sub.f=0.3 (PE/EA=10/1, v/v).

[0210] NMR spectrum:

[0211] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.03 (d, J=7.9 Hz, 1H), 7.89 (t, J=8.9 Hz, 2H), 7.60-7.52 (m, 3H), 7.47 (t, J=7.5 Hz, 1H), 6.35 (s, 1H), 5.80 (s, 1H), 5.70 (s, 2H), 4.17-4.09 (m, 1H), 3.31 (s, 1H), 2.81-2.59 (m, 2H);

[0212] .sup.13C NMR (100 MHz, CDCl.sub.3) δ 167.8, 134.9, 133.9, 131.8, 131.0, 130.5, 129.7, 128.95, 127.87, 126.86, 126.19, 125.40, 124.9 (q, J=280.8 Hz), 123.5, 69.9 (q, J=30.7 Hz), 65.8, 33.5;

[0213] .sup.19F NMR (375 MHz, CDCl.sub.3) δ −79.6 (d, J=6.0 Hz, 3F).

[0214] IR (ATR): 3444, 3049, 2937, 1707, 1633, 1413, 1320, 1271, 1167, 1126, 1029, 775 cm.sup.−1.

[0215] HRMS (ESI, m/z): a theoretically calculated value: C.sub.17H.sub.15F.sub.3NaO.sub.3.sup.+ (M+Na).sup.+: 347.0866; found: 347.0875.

Embodiment 18

N,N-diphenyl 5,5,5-trifluoro-4-hydroxy-2-methylenepentanamide

[0216] ##STR00031##

[0217] Under a nitrogen atmosphere, a magnetic stir bar was placed into a dry 10 mL Schlenk tube and Mn(OAc).sub.2.4H.sub.2O (14.7 mg, 0.06 mmol, 20 mol %), 7z (339.3 mg, 0.9 mmol, 3.0 eq.), DCM (3 mL, 0.1 M), 1a (70.2 mg, 0.3 mmol) and TBPB (145.7 mg, 0.75 mmol, 2.5 eq.) were added. Subsequently, the tube was sealed, and the mixture was heated to 70° C. and stirred for 14 h. After that, the Schlenk tube was placed in an ice-water bath of 5° C., and TBAF was added to be stirred for 0.5 h. The reaction mixture was quenched with water (2 mL) and subjected to extraction with DCM (3×10 mL). The organic phases were mixed and washed with brine, dried over Na.sub.2SO.sub.4, and evaporated to dryness by using a rotary evaporator. The crude product was purified by silica gel column chromatography (200×300-mesh) and eluted with PE/EA (8/1, v/v) to give 54 mg (yield 54%) of the target compound as a colorless oil. The product was tested, with the results as follows:

[0218] R.sub.f=0.27 (PE/EA=4/1, v/v).

[0219] NMR spectrum:

[0220] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.37 (t, J=7.8 Hz, 4H), 7.29-7.25 (m, 2H), 7.19-7.17 (m, 4H), 5.45 (s, 1H), 5.32 (s, 1H), 4.15-4.07 (m, 1H), 2.64-2.50 (m, 2H);

[0221] .sup.13C NMR (100 MHz, CDCl.sub.3) δ 172.4, 143.2, 138.6, 129.5, 127.3, 127.2, 125.8, 125.0 (q, J=280.3 Hz), 71.1 (q, J=30.7 Hz), 34.8;

[0222] .sup.19F NMR (375 MHz, CDCl.sub.3) δ −79.5 (d, J=6.0 Hz, 3F).

[0223] IR (ATR): 3288, 2963, 2930, 1644, 1592, 1491, 1364, 1275, 1163, 1126, 1029, 693 cm.sup.−1.

[0224] HRMS (ESI, m/z): a theoretically calculated value: C.sub.18H.sub.17F.sub.3NO.sub.2.sup.+ (M+H).sup.+: 336.1206; found: 336.1197.

Embodiment 19

N,N-dimethyl 5,5,5-trifluoro-4-hydroxy-2-methylenepentanamide

[0225] ##STR00032##

[0226] Under a nitrogen atmosphere, a magnetic stir bar was placed into a dry 10 mL Schlenk tube and Mn(OAc).sub.3.2H.sub.2O (16.1 mg, 0.06 mmol, 20 mol %), 7aa (227.9 mg, 0.9 mmol, 3.0 eq.), DCM (3 mL, 0.1 M), 1a (70.2 mg, 0.3 mmol) and TBPB (145.7 mg, 0.75 mmol, 2.5 eq.) were added. Subsequently, the tube was sealed, and the mixture was heated to 70° C. and stirred for 14 h. After that, the Schlenk tube was placed in an ice-water bath of 5° C., and TBAF was added to be stirred for 0.5 h. The reaction mixture was quenched with water (2 mL) and subjected to extraction with DCM (3×10 mL), and the organic phases were mixed and washed with brine, dried over Na.sub.2SO.sub.4, and evaporated to dryness by using a rotary evaporator. The crude product was purified by silica gel column chromatography (200×300-mesh) and eluted with PE/EA (10/1, v/v) to give 40 mg (63%) of the target compound as a yellow oil. The product was tested, with the results as follows:

[0227] R.sub.f=0.30 (PE/EA=2/1, v/v).

[0228] NMR spectrum:

[0229] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 5.58 (s, 1H), 5.37 (s, 1H), 4.10-4.02 (m, 1H), 3.14 (s, 3H), 3.03 (s, 3H), 2.64-2.41 (m, 2H);

[0230] .sup.13C NMR (100 MHz, CDCl.sub.3) δ 172.4, 137.6, 125.1 (q, J=280.3 Hz), 121.8, 71.1 (q, J=30.7 Hz), 39.8, 35.5, 34.8;

[0231] .sup.19F NMR (375 MHz, CDCl.sub.3) δ −79.4 (d, J=6.0 Hz, 3F).

[0232] IR (ATR): 3329, 2930, 1610, 1454, 1264, 1167, 1118, 1029, 734 cm.sup.−1

[0233] HRMS (ESI, m/z): a theoretically calculated value: C.sub.8H.sub.12F.sub.3NNaO.sub.2.sup.+ (M+Na).sup.+: 234.0712; found: 234.0707.

Embodiment 20

4-ene-4-(4-methylbenzenesulfonyl)-1,1,1-trifluoro-pentan-2-ol

[0234] ##STR00033##

[0235] Under a nitrogen atmosphere, a magnetic stir bar was placed into a dry 10 mL Schlenk tube and Mn(OAc).sub.3.2H.sub.2O (16.1 mg, 0.06 mmol, 20 mol %), 7ab (302.7 mg, 0.9 mmol, 3.0 eq.), DCM (3 mL, 0.1 M), 1a (70.2 mg, 0.3 mmol) and TBPB (145.7 mg, 0.75 mmol, 2.5 eq.) were added. Subsequently, the tube was sealed, and the mixture was heated to 70° C. and stirred for 14 h. After that, the Schlenk tube was placed in an ice-water bath of 5° C., and TBAF was added to be stirred for 0.5 h. The reaction mixture was quenched with water (2 mL) and subjected to extraction with DCM (3×10 mL). The organic phases were mixed and washed with brine, dried over Na.sub.2SO.sub.4, and evaporated to dryness by using a rotary evaporator. The crude product was purified by silica gel column chromatography (200×300-mesh) and eluted with PE/EA (20/1-10/1, v/v) to give 63.5 mg (yield 72%) of the target compound as a yellow oil. The product was tested, with the results as follows:

[0236] R.sub.f=0.30 (PE/EA=5/1, v/v).

[0237] NMR spectrum:

[0238] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.76 (d, J=8.4 Hz, 2H), 7.37 (d, J=8.0 Hz, 2H), 6.47 (s, 1H), 5.96 (s, 1H), 4.30-4.22 (m, 1H), 2.63-2.46 (m, 5H);

[0239] .sup.13C NMR (100 MHz, CDCl.sub.3) δ 145.5, 145.0, 134.7, 130.3, 128.6, 128.3, 124.6 (q, J=277.9 Hz), 69.1 (q, J=31.4 Hz), 31.2, 21.8;

[0240] .sup.19F NMR (375 MHz, CDCl.sub.3) δ −79.7 (d, J=6.0 Hz, 3F).

[0241] IR (ATR): 3474, 2930, 2855, 1595, 1431, 1279, 1137, 1081, 734 cm.sup.−1.

[0242] HRMS (ESI, m/z): a theoretically calculated value: C.sub.12H.sub.13F.sub.3NaO.sub.3S.sup.+ (M+Na).sup.+: 317.0430; found: 317.0432.

Embodiment 21

3-methyl-1-phenyl-3-(3,3,3-trifluoro-2-hydroxypropyl)indol-2-one

[0243] ##STR00034##

[0244] Under a nitrogen protection, Mn(OAc).sub.2.4H.sub.2O (29.4 mg, 0.12 mmol, 20 mol %) and 10a (170.7 mg, 0.72 mmol, 1.2 eq.) were added into a dry 25 mL Schlenk reaction tube containing a polytetrafluoroethylene magnetic stir bar with a suitable size, followed by addition of DCM (6 mL, 0.1 M), 1a (140.4 mg, 0.6 mmol) and TBPB (291.5 mg, 1.5 mmol, 2.5 eq.). The reaction tube was sealed, and then placed on a heating module, and the mixture was heated to 70° C. to be subjected to a reaction for 14 h. The reaction tube was taken down. After cooled to room temperature, the reaction tube was put into an ice water bath, and opened, TBAF (188.3 mg, 0.72 mmol, 1.2 eq.) was added, and then the reaction tube was sealed. The reaction was carried out under stirring in the ice water bath for 30 min, and quenched with 8 mL of water, and the reaction product was subjected to extraction with saturated NaCl (30 mL) and DCM (3×20 mL). The organic phases were mixed, then washed with saturated sodium chloride (2×50 mL), dried over anhydrous Na.sub.2SO.sub.4, filtered, and concentrated with a rotary evaporator under reduced pressure to obtain a crude product. The resulting crude product was separated by silica gel column chromatography with petroleum ether and ethyl acetate as an eluent to obtain 3-methyl-1-phenyl-3-(3,3,3-trifluoro-2-hydroxypropyl)indol-2-one (a total yield of two diastereoisomers is 910%). The product was tested, with the results as follows:

[0245] The diastereoisomer with larger polarity: R.sub.f=0.32 (PE/EA=5/1 v/v). mp: 116-118° C.

[0246] NMR spectrum:

[0247] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.54-7.49 (m, 2H), 7.43-7.39 (m, 3H), 7.26-7.22 (m, 2H), 7.16-7.12 (m, 1H), 6.85-6.82 (m, 1H), 3.66-3.57 (m, 1H), 2.53-2.22 (m, 2H), 1.91 (s, 1H), 1.54 (s, 3H).

[0248] .sup.13C NMR (150 MHz, CDCl.sub.3) δ 180.4, 143.8, 134.6, 131.6, 129.8, 128.6, 128.3, 126.8, 124.8 (q, J=282.2 Hz), 123.4, 122.9, 110.0, 68.7 (q, J=31.4 Hz), 46.1, 37.8, 25.8.

[0249] .sup.19F NMR (375 MHz, CDCl.sub.3) δ −80.0 (d, J=7.2 Hz, 3F).

[0250] IR (ATR): 3377, 3056, 2967, 2926, 1703, 1610, 1506, 1379, 1282, 1163, 1126, 1028, 854, 760 cm.sup.−1.

[0251] HRMS (ESI, m/z): a theoretically calculated value: C.sub.18H.sub.16F.sub.3NO.sub.2Na.sup.+ (M+Na).sup.+: 358.1025; found: 358.1012.

Embodiment 22

(E)-1,1,1-trifluoro-4-(2-fluorophenyl)-3-ene-butan-2-ol

[0252] ##STR00035##

[0253] Under a nitrogen atmosphere, a magnetic stir bar was placed into a dry 10 mL Schlenk tube and Mn(OAc).sub.3.2H.sub.2O (21.4 mg, 0.08 mmol, 20 mol %), 12a (132.8 mg, 0.8 mmol, 2.0 eq.), n-hexane (1 mL, 0.4 M), 1a (93.6 mg, 0.4 mmol) and TBPB (194.3 mg, 1.0 mmol, 2.5 eq.) were added. Subsequently, the tube was sealed, and the mixture was heated to 70° C. and stirred for 18 h. After that, the Schlenk tube was placed in a low temperature tank of −10° C., and TBAF was added to be stirred for 1.0 h. The reaction mixture was quenched with water (2 mL) and subjected to extraction with DCM (3×10 mL). The organic phases were mixed and washed with brine, dried over Na.sub.2SO.sub.4, and evaporated to dryness by using a rotary evaporator. The crude product was purified by silica gel column chromatography (200×300-mesh) and eluted with PE/EA (20/1, v/v) to give 64 mg (yield 73%) of the target compound as a white solid. The product was tested, with the results as follows:

[0254] R.sub.f=0.56 (PE/EA=4/1, v/v).

[0255] NMR spectrum:

[0256] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.47 (t, J=7.2 Hz, 1H), 7.31-7.26 (m, 1H), 7.15 7.00 (m, 3n), 6.31 (dd, J=16.2, 6.4 Hz, 1H), 4.69-4.63 (m, 1H), 2.44 (s, 1H);

[0257] .sup.13C NMR (100 MHz, CDCl.sub.3) δ 160.7 (d, J=250.5 Hz), 130.3 (d, J=8.7 Hz), 129.0 (d, J=2.9 Hz), 128.1 (d, J=2.9 Hz), 124.4 (q, J=273.4 Hz), 124.4 (d, J=3.9 Hz), 123.4, 123.4 (d, J=6.7 Hz), 116.1 (d, J=22.2 Hz), 71.9 (q, J=32.1 Hz);

[0258] .sup.19F NMR (375 MHz, CDCl.sub.3) δ −78.9 (d, J=6.0 Hz, 3F), −117.0-−117.0 (m, 1F).

[0259] IR (ATR): 3396, 2922, 1659, 1491, 1457, 1267, 1174, 1125, 969, 883, 753 cm.sup.−1.

[0260] HRMS (ESI, m/z): a theoretically calculated value: C.sub.10H.sub.6F.sub.4O.sup.− (M H).sup.−: 219.0439; found: 219.0441.

Embodiment 23

5,5-difluoro-1-phenyl-4-hydroxy-2-methylenepentan-1-one

[0261] ##STR00036##

[0262] Under a nitrogen protection, Mn(OAc).sub.3.2H.sub.2O (16.1 mg, 0.06 mmol, 20 mol %) and 7b (257.4 mg, 0.9 mmol, 3.0 eq.) were added into a dry 10 mL Schlenk reaction tube containing a polytetrafluoroethylene magnetic stir bar with a suitable size, followed by addition of DCM (3 mL, 0.1 M), 2a (64.8 mg, 0.3 mmol) and TBPB (145.7 mg, 0.75 mmol, 2.5 eq.). The reaction tube was sealed, and then placed on a heating module and the mixture was heated to 70° C. to be subjected to a reaction for 14 h. The reaction tube was taken down. After cooled to room temperature, the reaction tube was put into an ice water bath, and opened, and TBAF (1.0 M in THF, 0.36 mL, 0.36 mmol, 1.2 eq.) was added. The reaction tube was then sealed and placed in the ice water bath to be stirred for 30 min. The reaction was quenched with 2 mL of water, and the reaction solution was extracted with DCM (3×10 mL). The organic phases were mixed, washed with saturated sodium chloride (2×25 mL), dried with anhydrous Na.sub.2SO.sub.4, filtered, and concentrated with a rotary evaporator under reduced pressure to obtain a crude product. The resulting crude product was separated by silica gel column chromatography with petroleum ether and ethyl acetate as an eluent to obtain 5,5-difluoro-1-phenyl-4-hydroxy-2-methylenepentan-1-one as a colorless liquid (yield 80%). The product was tested, with the results as follows:

[0263] R.sub.f=0.25 (PE/EA=10/1, v/v).

[0264] NMR spectrum:

[0265] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.77 (d, J=7.3 Hz, 2H), 7.58 (t, J=7.3 Hz, 1H), 7.45 (t, J=7.6 Hz, 2H), 6.11 (s, 1H), 5.86-5.58 (m, 2H), 3.98-3.91 (m, 1H), 3.83 (s, 1H), 2.84-2.63 (m, 2H);

[0266] .sup.13C NMR (100 MHz, CDCl.sub.3) δ 199.5, 143.1, 137.0, 133.0, 130.9, 130.0, 128.5, 116.1 (t, J=244.2 Hz), 70.9 (t, J=24.1 Hz), 33.7;

[0267] .sup.19F NMR (375 MHz, CDCl.sub.3) δ −128.5-−131.2 (m, 2F).

[0268] IR (ATR): 3452, 3064, 2941, 2292, 2251, 1655, 1446, 1409, 1375, 1330, 1219, 1174, 1140, 1059, 947, 757 cm.sup.−1.

[0269] HRMS (ESI, m/z): a theoretically calculated value: C.sub.12H.sub.13F.sub.2O.sub.2.sup.+ (M+H).sup.+: 227.0878; found: 227.0871.

[0270] The method for preparing a difluoroethanolation reagent 2a used in the embodiment is as follows:

[0271] 1) 30 mmol of a compound 4 (the same as the compound 4 in Embodiment 1) and a solvent THF were added to a single-neck flask with a magnetic stirrer and the single-neck flask was placed in an ice bath of 0° C. Concentrated hydrochloric acid (10 eq.) was added dropwise to the reaction solution. After completion of adding dropwise, the reaction device was moved to a condition under room temperature and stirring was continued to be performed. After the reaction was completed, water was added to quench the reaction, followed by separation by column chromatography to obtain a compound 6.

[0272] 2) 10 mmol of the compound 6 and a solvent methanol (0.2 M) were added to a single-neck flask with a magnetic stirrer and the single-neck flask was placed in an ice bath of 0° C. Sodium borohydride solid (1.1 eq.) was added to the reaction system in three batches. After the reaction was completed, water was added to quench the reaction, followed by separation by column chromatography to obtain the difluoroethanolation reagent 2a.

[0273] NMR spectrum of the difluoroethanolation reagent 2a:

[0274] .sup.1H NMR (400 MHz, CDCl3) δ 7.57 (d, J=6.4 Hz, 2H), 7.45-7.39 (m, 3H), 5.39 (t, J=54.9 Hz, 1H), 0.62 (s, 6H);

[0275] .sup.13C NMR (100 MHz, CDCl3) δ 233.0 (t, J=32.0 Hz), 134.3, 132.4, 130.5, 128.4, 112.2 (t, J=249.9 Hz), −4.7;

[0276] .sup.19F NMR (375 MHz, CDCl3) δ −125.3 (d, J=53.6 Hz, 3F).

[0277] IR (ATR): 3071, 2960, 1670, 1428, 1252, 1118, 1044, 828, 787, 697 cm.sup.−1.

[0278] HRMS (ESI, m/z): a theoretically calculated value: C.sub.10H.sub.3F.sub.2OSi.sup.+ (M+H).sup.+: 215.0698; found: 215.0693.

Embodiment 24

[0279] Fluorinated Derivative of Diosgenin

##STR00037##

[0280] Under a nitrogen protection, Mn(OAc).sub.2.4H.sub.2O (14.7 mg, 0.06 mmol, 20 mol %) and 7am (373.5 mg, 0.6 mmol, 2.0 eq.) were added into a dry 10 mL Schlenk reaction tube containing a polytetrafluoroethylene magnetic stir bar with a suitable size, followed by addition of DCM (3 mL, 0.1 M), 2a (64.8 mg, 0.3 mmol) and TBPB (145.7 mg, 0.75 mmol, 2.5 eq.). The reaction tube was sealed and then placed on a heating module and the mixture was heated to 70° C. to be subjected to a reaction for 18 h. The reaction tube was taken down, allowed to cool to room temperature, placed in an ice water bath, and opened and then TBAF (1.0 M in THF, 0.36 mL, 0.36 mmol, 1.2 eq.) was added. The reaction tube was then sealed, and placed in an ice water bath to be stirred for 30 min. The reaction was then quenched with 2 mL of water, and the reaction solution was subjected to extraction with DCM (3×10 mL). The organic phases were mixed, then washed with saturated sodium chloride (2×25 mL), dried with anhydrous Na.sub.2SO.sub.4, filtered, and concentrated with a rotary evaporator under reduced pressure to obtain a crude product. The resulting crude product was separated by silica gel column chromatography with petroleum ether and ethyl acetate as an eluent to obtain the difluorinated derivative of diosgenin (yield 67%) as a white solid. The product was tested, with the results as follows:

[0281] R.sub.f=0.42 (PE/EA=5/1, v/v). mp: 126.1-127.4° C.

[0282] NMR spectrum:

[0283] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 6.29 (d, J=1.3 Hz, 1H), 5.84-5.52 (m, 2H), 5.39 (d, J=5.1 Hz, 1H), 4.74-4.61 (m, 1H), 4.40 (dd, J=14.3, 8.1 Hz, 1H), 3.98-3.84 (m, 1H), 3.50-3.43 (m, 1H), 3.36 (t, J=10.9 Hz, 1H), 2.69 (dd, J=14.4, 3.3 Hz, 1H), 2.51 (dd, J=14.4, 9.0 Hz, 1H), 2.37 (d, J=7.9 Hz, 2H), 2.06-1.40 (m, 18H), 1.02 (s, 3H), 0.96 (d, J=7.0 Hz, 3H), 0.78 (d, J=4.8 Hz, 6H);

[0284] .sup.13C NMR (100 MHz, CDCl.sub.3) δ 167.4, 139.5, 136.3, 122.8, 116.0 (t, J=244.3 Hz), 109.4, 80.9, 75.3, 70.6 (t, J=23.8 Hz), 67.0, 62.2, 56.6, 41.7, 40.4, 39.8, 38.1, 37.0, 36.9, 33.4 (t, J=4.0 Hz), 32.2, 32.0, 31.5, 28.9, 27.8, 20.9, 19.5, 17.2, 16.4, 14.6;

[0285] .sup.19F NMR (375 MHz, CDCl.sub.3) δ −128.7-−131.6 (m, 2F).

[0286] IR (ATR): 3418, 2945, 1710, 1454, 1375, 1327, 1245, 1051, 980, 83 cm.sup.−1.

[0287] HRMS (ESI, m/z): a theoretically calculated value: C.sub.33H.sub.48F.sub.3O.sub.5.sup.+ (M+H).sup.+: 563.3543; found: 563.3533.

Embodiment 25

Methyl 3-(3,3-difluoro-2-hydroxypropyl)-3-methyl-2-oxo-1-phenyldihydroindole-6-carboxylate

[0288] ##STR00038##

[0289] Under a nitrogen protection, Mn(OAc).sub.3.2H.sub.2O (16.1 mg, 0.06 mmol, 20 mol %) and 10i (83.4 mg, 0.36 mmol, 1.2 eq.) were added into a dry 10 mL Schlenk reaction tube containing a polytetrafluoroethylene magnetic stir bar with a suitable size, followed by addition of DCM (3 mL, 0.1 M), 2a (64.8 mg, 0.3 mmol) and TBPB (145.7 mg, 0.75 mmol, 2.5 eq.). The reaction tube was sealed and then placed on a heating module and the mixture was heated to 70° C. to be subjected to a reaction for 14 h. The reaction tube was taken down, allowed to cool to room temperature, placed in an ice water bath, and opened and TBAF (1.0 M in THF, 0.36 mL, 0.36 mmol, 1.2 eq.) was added. The reaction tube was then sealed, and placed in an ice water bath to be stirred for 30 min. Then the reaction was quenched with 2 mL of water, and the reaction solution was subjected to extraction with DCM (3×10 mL). The organic phases were mixed, washed with saturated sodium chloride and sodium carbonate, dried with anhydrous Na.sub.2SO.sub.4, filtered, and concentrated with a rotary evaporator under reduced pressure to obtain a crude product. The resulting crude product was separated by silica gel column chromatography with petroleum ether and ethyl acetate as an eluent to obtain methyl 3-(3,3-difluoro-2-hydroxypropyl)-3-methyl-2-oxo-1-phenyldihydroindole-6-carboxylate (yield 76%, 14h-a:14h-b=51:49). The product was tested, with the results as follows:

[0290] R.sub.f (14h-a)=0.28 (PE/EA=2/1, v/v). (36.8 mg, 39% yield, white solid, mp: 107.2-108.9° C.

[0291] NMR spectrum of 14h-a:

[0292] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.05 (dd, J=8.1, 1.7 Hz, 1H), 7.88 (s, 1H), 6.92 (d, J=8.2 Hz, 1H), 5.81-5.52 (m, 1H), 4.44 (s, 1H), 4.19-4.01 (m, 1H), 3.91 (s, 3H), 3.28 (s, 3H), 2.18-1.80 (m, 2H), 1.49 (s, 3H);

[0293] .sup.13C NMR (100 MHz, CDCl.sub.3) δ 182.4, 166.8, 146.4, 134.8, 131.2, 125.5, 123.9, 116.0 (t, J=240.6 Hz), 108.4, 68.6 (t, J=24.1 Hz), 52.3, 46.5, 36.0, 26.9, 22.6;

[0294] .sup.19F NMR (375 MHz, CDCl.sub.3) δ −124.8-−133.7 (m, 2F).

[0295] IR (ATR): 3414, 2926, 1703, 1498, 1457, 1286, 1103, 1051, 977, 772 cm.sup.−1.

[0296] HRMS (ESI, m/z): a theoretically calculated value: C.sub.15H.sub.18F.sub.2NO.sub.4.sup.+ (M+H).sup.+: 314.1198; found: 314.1198.

[0297] R.sub.f (14h-b)=0.17 (PE/EA=2/1, v/v). (34.5 mg, 37% yield, white solid, mp: 128.4-129.8° C.).

[0298] NMR spectrum of 14h-b:

[0299] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.05 (dd, J=8.1, 1.7 Hz, 1H), 6.92 (d, J=8.2 Hz, 1H), 5.81-5.52 (m, 1H), 4.43 (s, 1H), 4.21-4.07 (m, 1H), 3.91 (s, 3H), 3.27 (s, 3H), 2.23-1.76 (m, 1H), 1.49 (s, 3H);

[0300] .sup.13C NMR (100 MHz, CDCl.sub.3) δ 181.6, 167.0, 147.8, 132.5, 131.2, 124.7, 124.0, 115.8 (t, J=242.5 Hz), 108.1, 68.8 (t, J=23.8 Hz), 52.2, 45.9, 37.2, 26.7, 25.2;

[0301] .sup.19F NMR (375 MHz, CDCl.sub.3) δ −126.5-−133.0 (m, 2F).

[0302] IR (ATR): 3422, 2922, 1707, 1498, 1457, 1372, 1286, 1055, 977, 772 cm.sup.−1.

[0303] HRMS (ESI, m/z): theoretically calculated: C.sub.15H.sub.18F.sub.2NO.sub.4.sup.+ (M+H).sup.+: 314.1198; found: 314.1197.

Embodiment 26

(E)-4-(2,6-difluorophenyl)-1,1-difluorobut-3-en-2-ol

[0304] ##STR00039##

[0305] Under a nitrogen protection, Mn(OAc).sub.3.2H.sub.2O (16.1 mg, 0.06 mmol, 20 mol %) and 12d (110.4 mg, 0.6 mmol, 2.0 eq.) were added into a dry 10 mL Schlenk reaction tube containing a polytetrafluoroethylene magnetic stir bar with a suitable size, followed by addition of DCM (3 mL, 0.1 M), 2a (64.8 mg, 0.3 mmol) and TBPB (145.7 mg, 0.75 mmol, 2.5 eq.). The reaction tube was sealed and then placed on a heating module and the mixture was heated to 70° C. to be subjected to a reaction for 14 h. The reaction tube was taken down, allowed to cool to room temperature, placed in an ice water bath, and opened and TBAF (1.0 M in THF, 0.36 mL, 0.36 mmol, 1.2 eq.) was added. The reaction tube was then sealed and placed in an ice water bath to be stirred for 30 min. The reaction was then quenched with 2 mL of water, and the reaction solution was subjected to extraction with DCM (3×10 mL). The organic phases were mixed, washed with saturated sodium chloride and sodium carbonate, dried with anhydrous Na.sub.2SO.sub.4, filtered, and concentrated with a rotary evaporator under reduced pressure to obtain a crude product. The resulting crude product was separated by silica gel column chromatography with petroleum ether and ethyl acetate as an eluent to obtain (E)-4-(2,6-difluorophenyl)-1,1-difluorobut-3-en-2-ol (yield 60%) as a pale yellow liquid. The product was tested, with the results as follows:

[0306] R.sub.f=0.40 (PE/EA=5/1, v/v).

[0307] NMR spectrum:

[0308] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.24-7.16 (m, 1H), 6.94-6.84 (m, 3H), 6.59-6.53 (m, 1H), 5.89-5.59 (m, 1H), 4.48 (dq, J=10.3, 5.2 Hz, 1H), 2.23 (s, 1H);

[0309] .sup.13C NMR (150 MHz, CDCl.sub.3) δ 161.2 (dd, J=250.3, 7.3 Hz), 129.7-129.4 (m), 129.2 (t, J=10.8 Hz), 121.2, 115.5 (t, J=243.8 Hz), 113.4 (t, J=15.1 Hz), 111.7 (dd, J=21.5, 4.8 Hz), 72.8 (t, J=24.4 Hz);

[0310] .sup.19F NMR (375 MHz, CDCl.sub.3) δ −112.7 (s, 2F), −126.3-−130.0 (m, 2F).

[0311] IR (ATR): 3396, 2926, 1621, 1584, 1464, 1267, 1118, 1062, 999, 909 cm.sup.−1

[0312] HRMS (ESI, m/z): a theoretical value: C.sub.10H.sub.8F.sub.4ONa.sup.+ (M+Na).sup.+: 243.0404; found: 243.0412.

Embodiment 27

5,5,5-trifluoro-4-hydroxy-2-methylenepentanoic acid-5-formylpentyl Ester

[0313] ##STR00040##

[0314] Under a nitrogen atmosphere, a magnetic stir bar was placed into a dry 10 mL Schlenk tube and Mn(OAc).sub.2.4H.sub.2O (14.7 mg, 0.06 mmol, 20 mol %), 7a (152.4 mg, 0.6 mmol, 2.0 eq.), DCM (3 mL, 0.1 M), 1a (70.2 mg, 0.3 mmol) and TBPB (145.7 mg, 0.75 mmol, 2.5 eq.) were added. Subsequently, the tube was sealed, and the mixture was heated to 70° C. and stirred for 18 h. After that, the Schlenk tube was placed in an ice-water bath of 5° C., and TBAF was added to be stirred for 0.5 h. The reaction mixture was quenched with water (2 mL) and subjected to extraction with DCM (3×10 mL). The organic phases were mixed and washed with brine, dried over Na.sub.2SO.sub.4, and evaporated to dryness by using a rotary evaporator. The crude product was purified by silica gel column chromatography (200×300-mesh) and eluted with PE/EA (20/1-10/1, v/v) to give 39 mg (yield 46%) of the target compound as a colorless oil. The product was tested, with the results as follows:

[0315] R.sub.f=0.61 (PE/EA=2/1, v/v).

[0316] NMR spectrum:

[0317] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 9.77 (t, J=1.5 Hz, 1H), 6.33 (s, 1H), 5.80 (s, 1H), 4.22-4.09 (m, 3H), 2.79-2.57 (m, 2H), 2.47 (td, J=7.2, 1.3 Hz, 2H), 1.76-1.64 (m, 4H), 1.46-1.38 (m, 2H);

[0318] .sup.13C NMR (100 MHz, CDCl.sub.3) δ 202.5, 167.9, 135.2, 129.8, 124.9 (q, J=281.1 Hz), 69.9 (q, J=30.7 Hz), 65.3, 43.8, 33.5, 28.4, 25.6, 21.7;

[0319] .sup.19F NMR (375 MHz, CDCl.sub.3) δ −79.6 (d, J=6.0 Hz, 3F).

[0320] IR (ATR): 3425, 2930, 2859, 1711, 1275, 1167, 1126, 1029, 734 cm.sup.−1.

[0321] HRMS (ESI, m/z): a theoretically calculated value: C.sub.12H.sub.17F.sub.3NaO.sub.4.sup.+ (M+Na).sup.+: 305.0971; found: 305.0970.

Embodiment 28

[0322] Cholesterol Derivative

##STR00041##

[0323] Under a nitrogen atmosphere, a magnetic stir bar was placed into a dry 10 mL Schlenk tube and Mn(OAc).sub.2.4H.sub.2O (14.7 mg, 0.06 mmol, 20 mol %), 7ak (357.6 mg, 0.6 mmol, 2.0 eq.), DCM (3 mL, 0.1 M), 1a (70.2 mg, 0.3 mmol) and TBPB (145.7 mg, 0.75 mmol, 2.5 eq.) were added. Subsequently, the tube was sealed, and the mixture was heated to 70° C. and stirred for 18 h. After that, the Schlenk tube was placed in an ice water bath of 5° C., and TBAF was added to be stirred for 0.5 h. The reaction mixture was quenched with water (2 mL) and subjected to extraction with DCM (3×10 mL). The organic phases were mixed and washed with brine, dried over Na.sub.2SO.sub.4, and evaporated to dryness by using a rotary evaporator. The crude product was purified by silica gel column chromatography (200×300-mesh) and eluted with PE/EA (5/1, v/v) to give 53 mg (yield 71%) of the target compound as a yellow oil. The product was tested, with the results as follows:

[0324] R.sub.f=0.48 (PE/EA=8/1, v/v). mp: 83-85° C.

[0325] NMR spectrum:

[0326] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 6.33 (s, 1H), 5.78 (s, 1H), 5.40 (d, J=4.3 Hz, 1H), 4.73-4.65 (m, 1H), 4.12-4.09 (m, 1H), 3.75 (s, 1H), 2.77-2.57 (m, 2H), 2.37 (d, J=7.6 Hz, 2H), 2.03-1.95 (m, 2H), 1.92-1.79 (m, 3H), 1.70-1.43 (m, 7H), 1.40-1.25 (m, 4H), 1.20-1.08 (m, 7H), 1.03-0.95 (m, 6H), 0.91 (d, J=6.4 Hz, 3H), 0.86 (dd, J=6.7, 1.8 Hz, 6H), 0.68 (s, 3H);

[0327] .sup.13C NMR (100 MHz, CDCl.sub.3) δ 167.6, 139.4, 135.6, 129.6, 124.9 (q, J=280.8 Hz), 123.2, 75.64, 70.1 (q, J=30.7 Hz), 56.8, 56.2, 50.1, 42.4, 39.8, 39.6, 38.1, 37.0, 36.7, 36.3, 35.9, 33.6, 32.0, 31.9, 28.4, 28.1, 27.8, 24.4, 24.0, 23.0, 22.7, 21.2, 19.5, 18.8, 12.0;

[0328] .sup.19F NMR (375 MHz, CDCl.sub.3) δ −79.5 (bs, 3F).

[0329] IR (ATR): 3422, 2937, 2870, 1711, 1633, 1465, 1331, 1275, 1170, 1129, 1029, 734 cm.sup.−1.

[0330] HRMS (ESI, m/z): a theoretically calculated value: C.sub.33H.sub.51F.sub.3NaO.sub.3.sup.+ (M+Na).sup.+: 575.3683; found: 575.3671.

Embodiment 29

[0331] A method for synthesizing a compound L (1,1,1-trifluoro-3-ene-4-(2-methyl-3-(3-(3,4-dihydroxymethyl)phenyl)propyl)phenylbutan-2-ol) with anticancer activity and its difluorinated analogue M (1,1-difluoro-3-ene-4-(2-methyl-3-(3-(3,4-dihydroxymethyl)phenyl)propyl)phenylbutan-2-ol) based on the trifluoroethanolation reagent 1a or the difluoroethanolation reagent 2a. The reaction equation of the synthetic method may be expressed as follows:

##STR00042##

[0332] wherein R.sub.f is CF.sub.3— or HCF.sub.2—, and when R.sub.f is CF.sub.3—, the resulting product is the compound L with anticancer activity, and when R.sub.f is HCF.sub.2—, the resulting product is the difluorinated analogue M of the compound L.

[0333] Specifically, the synthetic method includes the following steps:

[0334] 1) A reactant 24 and triethylamine (1.4 eq.) were dissolved in a solvent DCM under nitrogen protection, and then the reaction was placed in a low temperature bath of −78° C., and trifluoromethanesulfonic anhydride (1.1 eq.) was added slowly dropwise. After completion of the adding dropwise, the reaction was quenched with a saturated aqueous ammonium chloride solution, and extraction was performed by DCM, followed by separation by column chromatography to obtain a compound 25;

[0335] 2) the compound 25 and tert-butyl acrylate (5 eq.), in the reaction system of palladium acetate (20% of the molar amount of the compound 25) and DPPP (1,3-bis(diphenylphosphino)propane, 22% of the molar amount of the compound 25) as a catalytic system, triethylamine (3.0 eq.) as a base, and DMF as a solvent, were stirred at 110° C. for 12 h. Water was added to quench the reaction, followed by extraction with ethyl acetate. The compound obtained by column chromatography was treated with trifluoroacetic acid in a solvent dichloromethane to obtain a compound 26;

[0336] 3) by using the reaction of the compound 26 with the trifluoroethanolation reagent 1a or the difluoroethanolation reagent 2a, Mn(OAc).sub.3.2H.sub.2O (16.1 mg, 0.06 mmol, 20 mol %) and 26 (0.6 mmol, 2.0 eq.) were added into a dry 10 mL Schlenk reaction tube containing a polytetrafluoroethylene magnetic stir bar with a suitable size, followed by addition of DCM (3 mL, 0.1 M), 1a or 2a (0.3 mmol) and TBPB (145.7 mg, 0.75 mmol, 2.5 eq.). The reaction tube was sealed, and then placed on a heating module and the mixture was heated to 70° C. to be subjected to a reaction for 14 h. The reaction tube was taken down and allowed to cool to room temperature, and then placed in an ice water bath, and opened and TBAF (1.0 M in THF, 0.36 mL, 0.36 mmol, 1.2 eq.) was added. The reaction tube was then sealed and placed in an ice water bath to be stirred for 30 min. The reaction was then quenched with 2 mL of water, and extraction was performed with DCM (3×10 mL), followed by separation by column chromatography to obtain the target product 27 or compound 28; and

[0337] (4) the compound 27 or compound 28 was dissolved in a dichloromethane solvent, and the reaction was placed in a low temperature tank of −78° C., and DIBAL-H (diisobutylaluminium hydride) was added slowly dropwise. After completion of adding dropwise, the reaction solution was slowly heated to 0° C., and the reaction was quenched with 3M HCl, followed by separation by column chromatography to obtain the compound L with anticancer activity or the difluorinated analogue M.

Embodiment 30

[0338] Ethyl 5,5,5-trifluoro-4-hydroxy-2-methylene pentanoate, with a synthetic route and a preparation method as follows:

##STR00043##

[0339] Under a nitrogen atmosphere, a magnetic stir bar was placed into a dry 10 mL Schlenk tube and Mn(OAc).sub.2.4H.sub.2O (14.7 mg, 0.06 mmol, 20 mol %), 7a (152.4 mg, 0.6 mmol, 2.0 eq.), DCM (3 mL, 0.1 M), A2 (0.3 mmol) and TBPB (145.7 mg, 0.75 mmol, 2.5 eq.) were added. Subsequently, the tube was sealed, and the mixture was heated to 70° C. and stirred for 18 h. After that, TBAF was added to the stirred material in an ice-water bath of 5° C. to be stirred for 0.5 h. The reaction mixture was quenched with water (2 mL) and subjected to extraction with DCM (3×10 mL), the organic phases were mixed and washed with brine, dried over Na.sub.2SO.sub.4, and evaporated to dryness by using a rotary evaporator. The crude product was purified by silica gel column chromatography (200×300-mesh) and eluted with PE/EA (20/1-10/1, v/v) (PE: petroleum ether, EA: ethyl acetate) to give 35 mg (yield 47%).

[0340] The preparation method of the trifluoroethanolation reagent A2 used in the embodiment was as follows:

[0341] 1) triethylchlorosilane (30 mmol), trifluoroethanol (30 mmol) and a tetrahydrofuran solvent were added to a dry single-neck flask with a magnetic stirrer, and the reaction flask was placed in a low-temperature tank of −78° C., and LDA (lithium diisopropylamide, 105 mmol) was added dropwise with a syringe pump. After completion of adding dropwise, the mixture was kept to be stirred for 4 h, heated to room temperature, and stirred again until the trifluoroethanol was completely consumed. Triethylchlorosilane was added at 0° C. to be stirred for 4 h, followed by separation by column chromatography to obtain a compound 4 (1,1-difluoro-2-triethylsilyl-2-triethylsiloxyethylene);

[0342] 2) a fluorinating agent Select-Fluor (2.0 eq.) and a mixed solvent of acetonitrile and dichloromethane (4:1, v/v) were added to a dry single-neck flask with a magnetic stirrer, and the single-neck flask was placed in an ice-water bath of 0° C. The compound 4 was added to the reaction, and after completion, the reaction solution was stirred at room temperature for 12 h. The reaction was quenched with water, followed by separation by column chromatography to obtain a compound 5 (trifluoroacetyltriethylsilane); and

[0343] 3) the compound 5 and methanol were added to a single-neck flask, and sodium borohydride solid was added to the reaction system in three batches. After the reaction was completed, water was added to quench the reaction, followed by separation by column chromatography to obtain the trifluoroethanolation reagent A2.

Embodiment 31

[0344] Ethyl 5,5,5-trifluoro-4-hydroxy-2-methylene pentanoate, using A3 as a raw material, with a synthetic route and a preparation method as follows:

##STR00044##

[0345] Under a nitrogen atmosphere, a magnetic stir bar was placed into a dry 10 mL Schlenk tube, and Mn(OAc).sub.2.4H.sub.2O (14.7 mg, 0.06 mmol, 20 mol %), 7a (152.4 mg, 0.6 mmol, 2.0 eq.), DCM (3 mL, 0.1 M), A3 (0.3 mmol) and TBPB (145.7 mg, 0.75 mmol, 2.5 eq.) were added. Subsequently, the tube was sealed, and the mixture was heated to 70° C. and stirred for 18 h. After that, TBAF was added to the stirred material in an ice-water bath of 5° C. to be stirred for 0.5 h. The reaction mixture was quenched with water (2 mL) and subjected to extraction with DCM (3×10 mL). The organic phases were mixed and washed with brine, dried over Na.sub.2SO.sub.4, and evaporated to dryness by using a rotary evaporator. The crude product was purified by silica gel column chromatography (200×300-mesh) and eluted with PE/EA (20/1-10/1, v/v) (PE: petroleum ether, EA: ethyl acetate) to give 25.4 mg (yield 34%).

[0346] The preparation method of the trifluoroethanolation reagent A3 used in the embodiment was as follows:

[0347] 1) triphenylsilyl chloride (30 mmol), trifluoroethanol (30 mmol), HMPA (3 mL) and a tetrahydrofuran solvent were added to a dry single-neck flask with a magnetic stirrer, and the reaction flask was placed in a low-temperature tank of −78° C., and LDA (lithium diisopropylamide, 105 mmol) was added dropwise with a syringe pump. After completion of adding dropwise, the mixture was kept to be stirred for 4 h, heated to room temperature, and then stirred again until trifluoroethanol was completely consumed. Triethylchlorosilane was added at 0° C. to be stirred for 4 h, followed by separation by column chromatography to obtain a compound 4 (1,1-difluoro-2-triphenylsilyl-2-triethylsiloxyethylene);

[0348] 2) a fluorinating agent Select-Fluor (2.0 eq.) and a mixed solvent of acetonitrile and dichloromethane (4:1, v/v) were added to a dry single-neck flask with a magnetic stirrer, and the single-neck flask was placed in an ice-water bath of 0° C. The compound 4 was added to the reaction, and after completion, the reaction solution was stirred at room temperature for 12 h. The reaction was quenched with water, followed by separation by column chromatography to obtain a compound 5 (trifluoroacetyltriphenylsilane); and

[0349] 3) the Compound 5 and methanol were added to a single-neck flask, and sodium borohydride solid was added to the reaction system in three batches. After the reaction was completed, water was added to quench the reaction, followed by separation by column chromatography to obtain the trifluoroethanolation reagent A3.

Embodiment 32

[0350] Ethyl 5,5,5-trifluoro-4-hydroxy-2-methylene pentanoate, using A4 as a raw material, with a synthetic route and a preparation method as follows:

##STR00045##

[0351] Under a nitrogen atmosphere, a magnetic stir bar was placed into a dry 10 mL Schlenk tube and Mn(OAc).sub.2.4H.sub.2O (14.7 mg, 0.06 mmol, 20 mol %), 7a (152.4 mg, 0.6 mmol, 2.0 eq.), DCM (3 mL, 0.1 M), A4 (0.3 mmol) and TBPB (145.7 mg, 0.75 mmol, 2.5 eq.) were added. Subsequently, the tube was sealed, and the mixture was heated to 70° C. and stirred for 18 h. After that, TBAF was added to the stirred material in an ice-water bath of 5° C. to be stirred for 0.5 h. The reaction mixture was quenched with water (2 mL) and subjected to extraction with DCM (3×10 mL). The organic phases were mixed and washed with brine, dried over Na.sub.2SO.sub.4, and evaporated to dryness by using a rotary evaporator. The crude product was purified by silica gel column chromatography (200×300-mesh) and eluted with PE/EA (20/1-10/1, v/v) (PE: petroleum ether, EA: ethyl acetate) to give 35.8 mg (yield 48%).

[0352] The preparation method of the trifluoroethanolation reagent A4 used in the embodiment was as follows:

[0353] 1) triphenylsilyl chloride (30 mmol), trifluoroethanol (30 mmol), HMPA (3 mL) and a tetrahydrofuran solvent were added to a dry single-neck flask with a magnetic stirrer, and the reaction flask was placed in a low-temperature tank of −78° C., and LDA (lithium diisopropylamide, 105 mmol) was added dropwise with a syringe pump. After completion of adding dropwise, the mixture was kept to be stirred for 4 h, heated to room temperature, and then stirred again until trifluoroethanol was completely consumed. Triethylchlorosilane was added at 0° C. to be stirred for 4 h, followed by separation by column chromatography to obtain a compound 4 (1,1-difluoro-2-methyldiphenylsilyl-2-triethylsiloxyethylene);

[0354] 2) a fluorinating agent Select-Fluor (2.0 eq.) and a mixed solvent of acetonitrile and dichloromethane (4:1, v/v) were added to a dry single-neck flask with a magnetic stirrer, and the single-neck flask was placed in an ice-water bath of 0° C. The compound 4 was added to the reaction, and after completion, the reaction solution was stirred at room temperature for 12 h. The reaction was quenched with water, followed by separation by column chromatography to obtain a compound 5 (trifluoroacetylmethyldiphenylsilane); and

[0355] 3) the compound 5 and methanol were added to a single-neck flask, and sodium borohydride solid was added to the reaction system in three batches. After the reaction was completed, water was added to quench the reaction, followed by separation by column chromatography to obtain the trifluoroethanolation reagent A4.

Embodiment 33

[0356] The storage stability, light stability and solubility in common solvents of the tri(di)fluoroethanolation reagents 1a, 2a, A2, A3 and A4 prepared in Embodiment 1, Embodiment 23, Embodiment 30, Embodiment 31 and Embodiment 32 of the present disclosure were tested, and the results are shown in Table 1 below.

TABLE-US-00001 TABLE 1 storage stability light stability sealed continuous sealed storage at white light storage at 5° C. for irradiation at 30° C. for two 25° C. for 2 solubility two weeks weeks days reagent sample dichloromethane (DCM) ethyl acetate (EA) acetonitrile n-hexane (degradation rate, mol %) a1 dissolved dissolved dissolved dissolved     5% <1% <1% a2 dissolved dissolved dissolved dissolved     4% <1% <1% A2 dissolved dissolved dissolved dissolved    14%   2% <1% A3 dissolved dissolved dissolved slightly   <1% <1% <1% soluble A4 dissolved dissolved dissolved well   3.2% <1% <1%