A method for asymmetric deuterium functionalization of olefins promoted by chiral thiols and deuterated water

Abstract

The present invention relates to a method for the asymmetric deuterium functionalization of alkenes promoted by chiral thiols and deuterated water. Specifically, the present invention provides a method for synthesizing compounds with high deuteration rates and high optical activity through visible light-catalyzed deuterium functionalization of alkenes, using inexpensive deuterated water as a deuterium source and a peptide- or sugar-derived thiol as a chiral source. The method has the advantages of a short synthetic route, simple operation, readily available deuterium sources, no metal requirements, broad substrate applicability, high deuteration rates and overall yields, and high enantioselectivity.

Description

Technical Field

[0001] The present invention relates to the field of asymmetric synthesis, and in particular provides a method for asymmetric deuterium functionalization of olefins promoted by chiral thiol and deuterated water. Background Art

[0002] In recent years, deuterated drugs have attracted increasing attention in the pharmaceutical industry. Deuterated drugs, also known as heavy drugs, deuterated drugs, or deuterium-containing drugs, are drugs obtained by replacing one or more carbon-hydrogen (CH) bonds at specific metabolic sites on drug molecules with carbon-deuterium (CD) bonds. This approach prolongs the drug's metabolic cycle, reduces the production of toxic metabolites and drug-drug interactions, thereby reducing dosage, improving safety, and achieving better efficacy. More importantly, the introduction of deuterium atoms into the chiral centers of some drug molecules can slow or prevent the isomerization process between the S and R configurations, thereby increasing the stability of the drug molecule and avoiding the potential adverse effects of the alternative isomer. Since the US Food and Drug Administration (FDA) approved the first deuterated drug, tetrabenazine (Austedo), for market entry in 2017, demand for deuterated drugs in the pharmaceutical industry has been increasing, and several deuterated compounds are currently in Phases I-III clinical trials. Therefore, a challenge facing organic synthetic chemists is how to efficiently synthesize chiral deuterated compounds, particularly those with deuterium atoms located at chiral centers. Unfortunately, to date, only a few asymmetric catalytic methods reported in the literature can introduce deuterium atoms into chiral centers, and they require the use of complex deuterium sources (Org.Lett.2012,14,3312; Nature 2016,540,414; J.Am.Chem.Soc.2017,139,11313) or the deuterated position is limited to the benzylic chiral center (iScience 2019,16,410; Org.Lett.2020,22,1204; Org.Lett.2020,22 8278).

[0003] Visible light photocatalysis has been a rapidly developing research area over the past decade. Compared to free radical reactions initiated by traditional free radical initiators, visible light photocatalysis offers advantages such as mild reaction conditions, good functional group compatibility, and the elimination of toxic initiators. In recent years, visible light photocatalytic deuteration methods promoted by deuterated water have emerged, providing new approaches for the synthesis of racemic α-deuterated tertiary amines or other achiral deuterated compounds. However, a highly enantioselective asymmetric deuteration method with a simple deuterium source and without the use of metals is still lacking in this field. Summary of the Invention

[0004] This invention overcomes the drawbacks of existing technologies, such as the need for a complex deuterium source, the prevalence of deuterated chiral centers at the benzylic position, and the need for transition metal catalysts. It provides a method for synthesizing highly deuterated and optically active compounds through visible light-catalyzed hydrogen functionalization of olefins using peptide- or sugar-derived thiols as chiral sources. Compared to traditional methods, this method offers advantages such as the absence of metals, the non-benzylic position of the deuterated chiral center, the inexpensive deuterium source, high yield and deuteration rate, and high enantioselectivity.

[0005] In a first aspect of the present invention, a method for preparing an optically active deuterated compound is provided, wherein the deuterated compound has the structural formula shown in Formula I below:

[0006]

[0007] in,

[0008] R 1 Select from the following groups:

[0009] R 2 and R 3 Each is independently selected from the following group: H, substituted or unsubstituted C1-C5 straight or branched alkyl, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted 5-7 membered heteroaryl, or R 2 and R 3 and the carbon atoms to which they are connected together form a 4-8 membered carbocyclic or heterocyclic ring (the carbocyclic or heterocyclic ring may be saturated or partially unsaturated);

[0010] M is selected from the group consisting of P, P(O), P(S), and P→(BH3);

[0011] Y is selected from the group consisting of O, CH2;

[0012] Z is selected from the following group: NR, O;

[0013] n is 0 or 1;

[0014] R 4 and R 5 Each is independently selected from the following group: substituted or unsubstituted C1-C5 straight chain or branched alkyl, substituted or unsubstituted C1-C5 straight chain or branched alkoxy, substituted or unsubstituted phenyl, substituted or unsubstituted C3-C8 cycloalkyl;

[0015] R 6 Selected from the following groups: substituted or unsubstituted phenyl, substituted or unsubstituted 5-7 membered heteroaryl; wherein, except for conventional substitution, the R 6 Optionally, it may include 1 substituent selected from the group consisting of: R 7 C(O)O-; the R7 Selected from the group consisting of substituted or unsubstituted phenyl, substituted or unsubstituted 5-7 membered heteroaryl, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted benzyl;

[0016] R is selected from the following group: H, substituted or unsubstituted C1-C5 straight or branched alkyl, substituted or unsubstituted phenyl;

[0017] In the formula, the configuration of the chiral deuterated center marked with * is R or S;

[0018] Unless otherwise specified, the substitution refers to the substitution of one or more hydrogen atoms on the group by a substituent selected from the group consisting of halogen, amino, hydroxy, nitro, cyano, trifluoromethyl, C1-C 12 Alkyl or cycloalkyl, C1-C 12 Alkoxy, oxygen atom (ie, =O), unsubstituted or replaced by C 1-4 Alkylamino-substituted C1-C 12 Alkylamino, C2-C6 ester, C2-C6 acyl, C2-C6 amide, thio C1-C 12 Alkyl, carboxyl, C5-C 12 Aryl or heteroaryl, C5-C 12 Heterocyclyl (containing 1-5, preferably 1-3 heteroatoms selected from N, O or S);

[0019] Characterized in that the method comprises the steps of:

[0020]

[0021] Under blue light (450-455 nm), in an organic solvent and deuterated water mixture, a photocatalyst and a chiral thiol are used to synergistically catalyze the reaction of compound 1 with compound 2 to obtain a compound of formula Ia or Ib;

[0022] wherein X is selected from the group consisting of H or Br;

[0023] The chiral thiol is selected from S1, S2, S3, S4, S5 or S6:

[0024]

[0025] In another preferred embodiment, the chiral thiol is selected from S3, S5 or S6.

[0026] In another preferred embodiment, in the reaction, the photocatalyst is 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile (4CzIPN), 2,4,6-tris(diphenylamino)-5-fluoroisophthalonitrile (3DPAFIPN), or 2,4,5,6-tetrakis(diphenylamino)isophthalonitrile (4DPAIPN), preferably 4DPAIPN or 4CzIPN.

[0027] In another preferred embodiment, in the reaction, the organic solvent is selected from the group consisting of benzene, toluene, tetrahydrofuran, p-xylene, o-xylene, m-xylene, mesitylene, or a combination thereof; preferably toluene.

[0028] In another preferred embodiment, in the reaction, the molar ratio of compound 1:compound 2 is 1 to 3:1.

[0029] In another preferred embodiment, in the reaction, the molar ratio of photocatalyst to compound 2 is 0.1 to 1:1; and / or

[0030] The molar ratio of chiral thiol: compound 2 is 0.1 to 1:1.

[0031] In another preferred embodiment, in the reaction, the volume ratio of the organic solvent to deuterated water is 1:1 to 5:1.

[0032] In another preferred embodiment, the reaction temperature is 0-50°C.

[0033] In another preferred embodiment, the reaction time is 72-120 hours.

[0034] In another preferred embodiment, the method further comprises: after the reaction is completed, purification through a short silica gel column to obtain a product with a high deuteration rate and high optical activity.

[0035] The second aspect of the present invention provides a method for preparing a 1,5-dihydroxy compound, characterized in that the method comprises the steps of:

[0036] The deuterated compound is prepared by the method according to the first aspect of the present invention, and

[0037]

[0038] In an organic solvent, in the presence of a base, the compound of formula I is subjected to ring opening to obtain a compound of formula II;

[0039] Wherein, the definition of each group is as described in the first aspect of the present invention.

[0040] In a third aspect of the present invention, there is provided an optically active deuterated compound having the structural formula shown in Formula I below:

[0041]

[0042] in,

[0043] R 1 Select from the following groups:

[0044] R 2 and R 3 Each is independently selected from the following group: H, substituted or unsubstituted C1-C5 straight or branched alkyl, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted 5-7 membered heteroaryl, or R 2 and R 3 and the carbon atoms to which they are connected together form a 4-8 membered carbocyclic or heterocyclic ring (the carbocyclic or heterocyclic ring may be saturated or partially unsaturated);

[0045] M is selected from the group consisting of P, P(O), P(S), and P→(BH3);

[0046] Y is selected from the group consisting of O, CH2;

[0047] Z is selected from the following group: NR, O;

[0048] n is 0 or 1;

[0049] R 4 and R 5 Each is independently selected from the following group: substituted or unsubstituted C1-C5 straight chain or branched alkyl, substituted or unsubstituted C1-C5 straight chain or branched alkoxy, substituted or unsubstituted phenyl, substituted or unsubstituted C3-C8 cycloalkyl;

[0050] R 6 Selected from the following groups: substituted or unsubstituted phenyl, substituted or unsubstituted 5-7 membered heteroaryl; wherein, except for conventional substitution, the R 6 Optionally, it may include 1 substituent selected from the group consisting of: R 7 C(O)O-; the R 7 Selected from the group consisting of substituted or unsubstituted phenyl, substituted or unsubstituted 5-7 membered heteroaryl, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted benzyl;

[0051] In the formula, the configuration of the chiral deuterated center marked with * is R or S;

[0052] Unless otherwise specified, the substitution refers to the substitution of one or more hydrogen atoms on the group by a substituent selected from the group consisting of halogen, amino, hydroxy, nitro, cyano, trifluoromethyl, C1-C 12 Alkyl or cycloalkyl, C1-C 12Alkoxy, oxygen atom (ie, =O), unsubstituted or replaced by C 1-4 Alkylamino-substituted C1-C 12 Alkylamino, C2-C6 ester, C2-C6 acyl, C2-C6 amide, thio C1-C 12 Alkyl, carboxyl, C5-C 12 Aryl or heteroaryl, C5-C 12 Heterocyclic group (containing 1-5, preferably 1-3 heteroatoms selected from N, O or S).

[0053] A fourth aspect of the present invention provides a deuterated compound having a structural formula shown in Formula Ia or Ib below:

[0054]

[0055] In another preferred embodiment, the deuterated compound is selected from the following group:

[0056]

[0057] It should be understood that within the scope of the present invention, the above-mentioned technical features of the present invention and the technical features described in detail below (such as in the embodiments) can be combined with each other to form new or preferred technical solutions. Due to space limitations, they will not be listed here one by one. BRIEF DESCRIPTION OF THE DRAWINGS

[0058] Figure 1 For chiral compound 3 1 H NMR spectrum;

[0059] Figure 2 For the racemic non-deuterated compound 3 1 H NMR spectrum;

[0060] Figure 3 For chiral compound 3 13 C NMR spectrum;

[0061] Figure 4 is the high performance liquid chromatogram of racemic compound 3;

[0062] Figure 5 This is the high performance liquid chromatogram of chiral compound 3. DETAILED DESCRIPTION

[0063] After extensive and in-depth research, the inventors have developed a simple and efficient method for synthesizing chiral deuterated compounds with high deuteration rates and high optical activity. This method utilizes inexpensive deuterated water as a deuterium source and a peptide sugar-derived thiol as a chiral source. This novel method utilizes visible light-catalyzed hydrogen functionalization of olefins to synthesize chiral deuterated compounds with high deuteration rates and high optical activity. Compared to traditional methods, this method offers advantages such as being metal-free, non-benzyl deuterated chiral centers, a low-cost deuterium source, high yields and deuteration rates, and high enantioselectivity.

[0064] Asymmetric deuterium functionalization of alkenes promoted by chiral thiols and deuterated water

[0065] The object of the present invention is to provide a method for constructing a compound with high deuteration rate and high optical activity by utilizing asymmetric deuterium functionalization reaction of olefins promoted by chiral thiol and deuterated water.

[0066] The present invention provides a method for preparing a chiral deuterated compound with a high deuteration rate and high optical activity, wherein the chiral deuterated compound has the following structural formula:

[0067]

[0068] in,

[0069] R 1 Select from the following groups:

[0070] R 2 and R 3 Each is independently selected from the following group: H, substituted or unsubstituted C1-C5 straight or branched alkyl, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted 5-7 membered heteroaryl, or R 2 and R 3 and the carbon atoms to which they are connected together form a 4-8 membered carbocyclic or heterocyclic ring (the carbocyclic or heterocyclic ring may be saturated or partially unsaturated);

[0071] M is selected from the group consisting of P, P(O), P(S), and P→(BH3);

[0072] Y is selected from the group consisting of O, CH2;

[0073] Z is selected from the following group: NR, O;

[0074] n is 0 or 1;

[0075] R 4 and R 5Each is independently selected from the following group: substituted or unsubstituted C1-C5 straight chain or branched alkyl, substituted or unsubstituted C1-C5 straight chain or branched alkoxy, substituted or unsubstituted phenyl, substituted or unsubstituted C3-C8 cycloalkyl;

[0076] R 6 Selected from the following groups: substituted or unsubstituted phenyl, substituted or unsubstituted 5-7 membered heteroaryl; wherein, except for conventional substitution, the R 6 Optionally, it may include 1 substituent selected from the group consisting of: R 7 C(O)O-; the R 7 Selected from the group consisting of substituted or unsubstituted phenyl, substituted or unsubstituted 5-7 membered heteroaryl, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted benzyl;

[0077] R is selected from the following group: H, substituted or unsubstituted C1-C5 straight or branched alkyl, substituted or unsubstituted phenyl;

[0078] In the formula, the configuration of the chiral deuterated center marked with * is R or S;

[0079] Unless otherwise specified, the substitution refers to the substitution of one or more hydrogen atoms on the group by a substituent selected from the group consisting of halogen, amino, hydroxy, nitro, cyano, trifluoromethyl, C1-C 12 Alkyl or cycloalkyl, C1-C 12 Alkoxy, oxygen atom (ie, =O), unsubstituted or replaced by C 1-4 Alkylamino-substituted C1-C 12 Alkylamino, C2-C6 ester, C2-C6 acyl, C2-C6 amide, thio C1-C 12 Alkyl, carboxyl, C5-C 12 Aryl or heteroaryl, C5-C 12 Heterocyclyl (containing 1-5, preferably 1-3 heteroatoms selected from N, O or S);

[0080] The deuterium water-promoted asymmetric deuterium functionalization reaction of olefins to construct chiral deuterated compounds with high deuteration rate and high optical activity is as follows:

[0081]

[0082] Wherein, the definitions of each group are as described above. The method comprises:

[0083] Under blue light (450-455 nm) irradiation conditions, in an organic solvent and deuterated water mixture at 0-50 ° C, a photocatalyst and a chiral thiol are used to synergistically catalyze the reaction of compound 1 and compound 2 for 72-120 hours. After the reaction, a product with a high deuteration rate and high optical activity can be obtained after passing through a short silica gel column; wherein the molar ratio of the photocatalyst: chiral thiol: 1:2 is 0.1-1:0.1-1:1-3:1, and the volume ratio of the organic solvent / deuterated water is 1:1-5:1; the photocatalyst is 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile (4CzIPN), 2,4,6-tris(diphenylamino)-5-fluoroisophthalonitrile Isophthalonitrile (3DPAFIPN), 2,4,5,6-tetrakis(diphenylamino)isophthalonitrile (4DPAIPN), preferably 4DPAIPN or 4CzIPN; the chiral thiol is S1-S6, preferably S3, S5 or S6; the compound 1 is a diaryl(alkyl) phosphine oxide compound (R2P(O)H), an organosilane (R3SiH) or an alkyl bromide substrate containing a difluoro functional group (RCF2Br); the compound 2 is a lactone or lactam olefin having an exocyclic double bond of a six-membered ring or a five-membered ring; the organic solvent is benzene, toluene, chlorobenzene, p-xylene, o-xylene, m-xylene or mesitylene; preferably toluene.

[0084] In another preferred embodiment, a photocatalyst, an olefin, a chiral thiol, a diaryl (alkyl) phosphine oxide compound (R2P(O)H) or an organosilane (R3SiH) or an alkyl bromide substrate containing a difluoro functional group (RCF2Br), a dry organic solvent, and deuterated water are added to a dry reactor and stirred at 0-50°C for 72-120 hours. After the reaction is completed, water is added to the reaction system for washing, and the organic solvent is extracted. The organic phases are combined, washed with saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to obtain a compound with a high deuteration rate and high optical activity.

[0085] Compared with the prior art, the main advantages of the present invention include:

[0086] 1. The method of the present invention uses polypeptide or sugar-derived thiols as chiral sources and uses visible light-catalyzed hydrogen functionalization of olefins to prepare deuterated compounds. The method is simple and efficient, with a high deuteration rate, and the resulting products have high optical activity.

[0087] 2. The chiral deuterated compounds prepared by the method of the present invention can be conveniently converted into 1,5-dihydroxy compounds with central chirality and completely preserved chirality and deuteration rate, and can be further converted to obtain monohydroxy products by removing the silicon group, or selectively removing the silicon-based protecting group to hydrogen or hydroxyl, thereby synthesizing a series of pharmaceutical compounds with deuterated chiral center structural units.

[0088] 3. The method of the present invention has the advantages of a short synthetic route, simple operation, readily available raw materials, no need for the use of metals, wide substrate universality, high deuteration rate and total yield, and high enantioselectivity. It overcomes the defects of the prior art such as long synthetic steps, low yield, harsh reaction conditions, and inconvenient operation.

[0089] The present invention will be further described below in conjunction with specific examples. It should be understood that these examples are intended to illustrate the present invention only and are not intended to limit the scope of the invention. The experimental methods in the following examples, for which specific conditions are not specified, are generally based on conventional conditions or the conditions recommended by the manufacturer. Unless otherwise stated, percentages and parts are calculated by weight.

[0090] Example 1

[0091]

[0092] Here, equiv means equivalent, and mol means mole.

[0093] To a dry reaction flask (16×60 mm) were added 4DPAIPN (1.8 mg, 0.002 mmol), chiral thiol S3 (21.9 mg, 0.03 mmol), 1a (103.8, 0.4 mmol), dry toluene (1.5 mL), deuterated water (0.5 mL), and olefin 2a (28.0 mg, 0.2 mmol) in sequence. The air in the reaction flask was then replaced with nitrogen for 2 minutes, the reaction system was sealed, and the reaction was carried out at 10°C under blue light for 72 h. After the reaction, 5 mL of water and 10 mL of dichloromethane were added to the system, the organic layer was separated, and the aqueous layer was extracted with dichloromethane (10 mL × 3). The organic layers were combined, washed with saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography (petroleum ether / dichloromethane / diethyl ether = 14 / 10 / 1) to give a solid chiral deuterated compound 3 (70.0 mg, 87%, 96% D) with high optical activity: 95:5er (HPLC conditions: Chiralcel AD-H column, n-hexane / isopropanol = 98.5 / 1.5, 1 mL / min, λ = 214 nm, t1 (small peak) = 13.0 min, t2 (large peak) = 16.4 min); [α] 25 D =-68.8 (c=0.50, CHCl3); mp85-87℃; 1H NMR (400MHz, CDCl3) δ = 7.68-7.54 (m, 6H), 7.46-7.31 (m, 9H), 4.11 (dd, J1 = 11.6Hz, J2 = 2.4Hz, 0 .04H),2.51-2.31(m,2H),1.78(d,J=15.2Hz,1H),1.65-1.52(m,3H),1.00(s,3H),0.92(s,3H); 13 C NMR (100MHz, CDCl3) δ = 170.9, 135.9, 134.5, 129.5, 127.8, 84.2 (t, J C-D =21.9Hz),34.0,33.0,27.4,26.5,19.3,14.9; HRMS[M+Na + Calculated value: 424.1814, measured value: 424.1811.

[0094] The hydrogen spectrum of the compound is Figure 1 As shown in Figure 3 As shown in the results, the product's proton spectrum is clearly distinct from that of the non-deuterated form, suggesting the formation of a deuterated compound with a deuteration rate of 96%. High-resolution mass spectrometry further confirmed the molecular weight of the deuterated product.

[0095] HPLC analysis of the product Figure 5 As shown in the results, the deuterated product was generated with an enantiomeric ratio of 95:5

[0096] Example 2

[0097]

[0098] The procedure was carried out in accordance with Example 1. 4-DPAIPN (2.0 mg, 0.002 mmol), 1a (104.4 mg, 0.4 mmol), chiral thiol S3 (21.9 mg, 0.03 mmol), dry toluene (1.5 mL), deuterated water (0.5 mL), and olefin 2b (36.3 mg, 0.2 mmol) were purified by column chromatography (petroleum ether / ethyl acetate = 5 / 1) to afford a highly optically active solid chiral deuterated compound 4 (74.8 mg, 84%, 95% D): 96:4er (HPLC conditions: Chiralcel OD-H column, n-hexane / isopropanol = 98.5 / 1.5, 1 mL / min, λ = 214 nm, t1 (large peak) = 11.8 min, t2 (small peak) = 13.3 min); [α] D 25 =-65.3°(c=0.21,CHCl3); mp99-101℃; 1H NMR (400MHz, CDCl3) δ = 7.64-7.51 (m, 6H), 7.47-7.28 (m, 9H), 4.16 (dd, J1 = 11.4H z, J2=2.2Hz,0.05H),2.46-2.14(m,2H),1.95-1.75(m,2H),1.67-1.05(m,12H); 13 CNMR (100MHz, CDCl3); δ=171.3,135.9,134.4,129.5,127.9,35.9,33.3,29.2,26.7,26.4,26.0,21.3,20.9,14.4; HRMS C 29 H 31 DNaO2Si[M+Na + Calculated value: 464.2127, predicted value: 464.2126.

[0099] Example 3

[0100]

[0101] The procedure was carried out in accordance with Example 1. 4-DPAIPN (2.0 mg, 0.002 mmol), 1a (104.2 mg, 0.4 mmol), chiral thiol S3 (22.2 mg, 0.03 mmol), dry toluene (1.5 mL), deuterated water (0.5 mL), and olefin 2c (37.1 mg, 0.2 mmol) were purified by column chromatography (petroleum ether / ethyl acetate = 3 / 2) to afford a highly optically active solid chiral deuterated compound 5 (74.7 mg, 83%, 93% D): 98:2er (HPLC conditions: Chiralcel AD-H column, n-hexane / isopropanol = 95 / 5, 1 mL / min, λ = 214 nm, t1 (minor peak) = 14.0 min, t2 (major peak) = 15.3 min); [α] D 25 =-62.4°(c=0.21,CHCl3); mp139-141℃; 1H NMR (400MHz, CDCl3) δ = 7.64-7.52 (m, 6H), 7.47-7.32 (m, 9H), 4.17 (dd, J1 = 11.6Hz, J2 = 2.4Hz, 0.07H), 3.87-3.72 (m, 2H), 3.61-3.43 (m, 2H), 2.46 -2.26(m,2H),2.02-1.90(m,1H),1.87-1.72(m,3H),1.71-1.56(m,2H),1.33(dd,J1=13.6Hz,J2=2.4Hz,1H),1.15(dd,J1=13.4Hz,J2=2.2Hz,1H); 13 C NMR (100MHz, CDCl3) δ = 170.7, 135.7, 134.1, 129.6, 127.9, 83.4 (t, J C-D =22.2Hz),63.1,63.0,34.2,33.2,30.2,26.3,25.7,14.3; HRMS(ESI)C 28 H 29 DNaO3Si[M+Na + Calculated value: 466.1919, measured value: 466.1917.

[0102] Example 4

[0103]

[0104] The procedure was carried out in accordance with Example 1. 4CzIPN (4.1 mg, 0.005 mmol), 1a (104.2 mg, 0.4 mmol), chiral thiol S3 (22.1 mg, 0.03 mmol), dry toluene (1.5 mL), deuterated water (0.5 mL), and olefin 2d (33.4 mg, 0.2 mmol) were purified by column chromatography (petroleum ether / dichloromethane / diethyl ether = 14 / 10 / 1) to give a highly optically active solid chiral deuterated compound 6 (72.0 mg, 84%, 94% D): 95:5er (HPLC conditions: Chiralcel AD-H column, n-hexane / isopropanol = 95 / 5, 1 mL / min, λ = 214 nm, t1 (large peak) = 8.3 min, t2 (small peak) = 9.0 min); [α] D 25 =-61.0°(c=0.50,CHCl3); mp115-118℃; 1H NMR (500MHz, CDCl3) δ = 7.63-7.53 (m, 6H), 7.45-7.32 (m, 9H), 4.32 (dd, J1 = 11.5Hz, J2 = 2. 5Hz,0.06H),2.51-2.39(m,2H),1.90-1.78(m,2H),1.72-1.48(m,8H),1.42-1.32(m,2H); 13 C NMR (100MHz, CDCl3)δ=170.7,135.9,134.4,129.6,127.9,45.1,36.1,32.4,30.8,27.5,25.4,25.0,16.5; HRMS C 28 H 29 DNaO2Si[M+Na + Calculated value: 450.1970, measured value: 450.1971.

[0105] Example 5

[0106]

[0107] The procedure was performed in accordance with Example 1. 4CzIPN (4.2 mg, 0.005 mmol), 1a (104.9 mg, 0.4 mmol), chiral thiol S3 (22.2 mg, 0.03 mmol), dry toluene (1.5 mL), deuterated water (0.5 mL), and olefin 2e (53.9 mg, 0.2 mmol) were added. Column chromatography (petroleum ether / dichloromethane / diethyl ether = 14 / 10 / 1) afforded the highly optically active solid chiral deuterated compound 7 (105.2 mg, 98%, 94% D): >99:1 er (HPLC conditions: Chiralcel OD-H column, n-hexane / isopropanol = 90 / 10, 1 mL / min, λ = 214 nm, t1 (large peak) = 6.7 min, t2 (small peak) = 8.7 min); [α] D 25 =-192.0°(c=0.50,CHCl3); mp72-74℃; 1 H NMR (400MHz, CDCl3) δ = 7.49-7.12 (m, 23H), 7.00 (d, J = 7.6Hz, 2H), 5.38 (d, J = 10.8Hz, 0.06H), 2.97- 2.84(m,1H),2.56-2.40(m,2H),2.15-2.00(m,1H),1.75(d,J=15.2Hz,1H),1.25(d,J=15.2Hz,1H); 13HRMS C 36 H 31 DNaO2Si[M+Na + Calculated value: 548.2127, measured value: 548.2125.

[0108] Example 6

[0109]

[0110] The procedure was performed in accordance with Example 1. 4CzIPN (4.1 mg, 0.005 mmol), 1a (105.3 mg, 0.4 mmol), chiral thiol S3 (22.2 mg, 0.03 mmol), dry toluene (1.5 mL), deuterated water (0.5 mL), and olefin 2f (58.7 mg, 0.2 mmol) were added. Column chromatography (petroleum ether / dichloromethane / diethyl ether = 14 / 10 / 1) afforded the highly optically active solid chiral deuterated compound 8 (108.2 mg, 97%, 94% D): >99:1 er (HPLC conditions: Chiralcel OD-H column, n-hexane / isopropanol = 90 / 10, 1 mL / min, λ = 214 nm, t1 (large peak) = 5.4 min, t2 (small peak) = 7.3 min); [α] D 25 =-181.0°(c=0.50,CHCl3); mp82-84℃; 1 H NMR (400MHz, CDCl3) δ = 7.51-7.28 (m, 15H), 7.08-6.97 (m, 6H), 6.88 (d, J = 8.0Hz, 2H), 5.33 (d, J = 11.2Hz, 0.06H), 2.92- 2.76(m,1H),2.52-2.36(m,2H),2.35-2.18(m,6H),2.16-2.00(m,1H),1.74(d,J=15.2Hz,1H),1.29(d,J=15.2Hz,1H); 13 CNMR(100MHz, CDCl3)δ=169.3,141.5,140.9,136.2,136.1,135.8,134.1,129.5,129.32,129.30,127.8,127.4,127.2,81.6(t,J C-D=18.4Hz),48.4,27.5,26.6,20.9,20.8,17.6; HRMS C 38 H 35 DNaO2Si[M+Na + Calculated value: 576.2440, measured value: 576.2434.

[0111] Example 7

[0112]

[0113] The procedure was performed in accordance with Example 1. 4CzIPN (4.2 mg, 0.005 mmol), 1a (104.3 mg, 0.4 mmol), chiral thiol S3 (22.3 mg, 0.03 mmol), dry toluene (1.5 mL), deuterated water (0.5 mL), and olefin 2 g (60.5 mg, 0.2 mmol) were added. Column chromatography (petroleum ether / dichloromethane / diethyl ether = 14 / 10 / 1) afforded a highly optically active solid chiral deuterated compound 9 (111.2 mg, 97%, 92% D): >99:1 er (HPLC conditions: Chiralcel OD-H column, n-hexane / isopropanol = 95 / 5, 1 mL / min, λ = 214 nm, t1 (large peak) = 10.0 min, t2 (small peak) = 11.2 min); [α] D 25 =-149.8°(c=0.51,CHCl3); mp97-102℃; 1 H NMR (400MHz, CDCl3) δ=7.50-7.28(m,15H),7.17-7.06(m,2H),6.99-6.85(m,6H),5.28(d,J=11.2Hz,0.08H ),2.97-2.77(m,1H),2.64-2.30(m,2H),2.20-1.96(m,1H),1.74(d,J=15.2Hz,1H),1.22(d,J=15.2Hz,1H); 13 C NMR (100MHz, CDCl3) δ = 168.5, 162.6 (d, J C-F =6.6Hz),160.1(d,J C-F =6.4Hz),139.6(dd,J1=34.8Hz,J2=3.3Hz),135.7,133.7,129.7,129.3(d,J C-F =7.8Hz),128.9(d,J C-F=7.8Hz), 127.9, 115.6 (dd, J1 = 21.2Hz, J2 = 1.6Hz), 48.3, 27.3, 26.9, 17.8; 19 F NMR (376MHz, CDCl3) δ = -115.0, -115.3; HRMS C 36 H 29 DF2NaO2Si[M+Na + Calculated value: 584.1938, measured value: 584.1935.

[0114] Example 8

[0115]

[0116] The operation was carried out in accordance with Example 1. 4CzIPN (4.0 mg, 0.005 mmol), 1a (104.4 mg, 0.4 mmol), chiral thiol S3 (21.9 mg, 0.03 mmol), dry toluene (1.5 mL), deuterated water (0.5 mL), olefin 2h (40.7 mg, 0.2 mmol). Column chromatography (petroleum ether / dichloromethane / diethyl ether = 14 / 10 / 1) gave a highly optically active solid chiral deuterated compound 10 (90.9 mg, 96%, 96% / 94% D): >99:1 / 95:5 er, dr = 1:1.2 (HPLC conditions: Chiralcel OD-H column, n-hexane / isopropanol = 99.8 / 0.2, 1 mL / min, λ = 214 nm, t1 = 39.0 min, t2 = 41.5 min, t3 = 45.5 min, t4 = 50.3 min); [α] D 25 =-38.1°(c=0.22,CHCl3); mp56-58℃; 1 H NMR (400MHz, CDCl3) δ = 7.75-7.00 (m, 35H), 4.69 (d, J = 10.4Hz, 0.04H), 4.47 ( dd, J1=11.4Hz, J2=2.2Hz, 0.06H), 2.66-2.39(m, 3.5H), 2.38-2.12(m, 1.8H), 2.02-1.87(m,1H),1.83-1.73(m,0.8H),1.69(d,J=15.2Hz,0.8H),1.58(d,J =15.2Hz,1.0H),1.44(s,2.4H),1.39-1.29(4.0H),1.20(d,J=15.2Hz,0.8H); 13C NMR (100MHz, CDCl3) δ = 171.3, 171.0, 145.1, 144.0, 135.78, 135.75, 134.19, 134.17, 129.51, 129.46, 128.7, 128.5, 127. 80,127.75,126.8,126.7,126.6,125.9,84.3-82.6(m),40.9,40.8,35.0,31.8,28.0,27.5,25.3,17.3,16.2,14.5; HRMS C 31 H 29 DNaO2Si[M+Na + Calculated value: 486.1970, measured value: 486.1962.

[0117] Example 9

[0118]

[0119] The operation was carried out in accordance with Example 1. 4-DPAIPN (2.0 mg, 0.002 mmol), 1a (104.7 mg, 0.4 mmol), chiral thiol S3 (21.9 mg, 0.03 mmol), dry toluene (1.5 mL), deuterated water (0.5 mL), and olefin 2i (38.5 mg, 0.2 mmol) were reacted for 96 h. Column chromatography (petroleum ether / dichloromethane / diethyl ether = 14 / 10 / 1) gave a highly optically active liquid chiral deuterated compound 11 (63.8 mg, 70%, 97% / 97% D): 98:2 / 96:4 er, dr = 1:1.5 (HPLC conditions: Chiralcel OD-H column, n-hexane / isopropanol = 99.2 / 0.8, 1 mL / min, λ = 214 nm, t1 = 24.3 min, t2 = 27.3 min, t3 = 34.4 min, t4 = 43.0 min); [α] D 25 =-50.0°(c=0.24,CHCl3); 1H NMR (400MHz, CDCl3) δ = 7.85-7.10 (m, 34H), 6.43-6.23 (m, 1.8H), 6.16 (d, J = 3.2Hz, 1H), 6.12 (d, J = 3.2Hz, 0.8H), 4.69 (dd, J1 = 11.4Hz, J2 = 1.4Hz, 0.03H ),4.31(dd,J1=11.4Hz,J2=2.6Hz,0.03H),2.70-2.24(m,5H),2.21-2.10(m ,1.0H),1.85-1.64(m,4.0H),1.53(d,J=15.2Hz,1.0H),1.43-1.20(m,7H); 13 C NMR (100MHz, CDCl3) δ = 170.9, 170.7, 158.0, 156.4, 142.0, 141.8, 135.80, 135.78, 134.4, 134.2, 129.47, 129.4 6,127.78,127.77,110.2,109.9,107.1,106.1,39.0,38.9,31.7,31.6,27.6,27.2,23.3,16.5,15.8,14.8; HRMS C 29 H 27 DNaO3Si[M+Na + Calculated value: 476.1763, measured value: 476.1765.

[0120] Example 10

[0121]

[0122] The operation was carried out in accordance with Example 1. 4-DPAIPN (1.6 mg, 0.002 mmol), 1a (104.5 mg, 0.4 mmol), chiral thiol S3 (21.8 mg, 0.03 mmol), dry toluene (1.5 mL), deuterated water (0.5 mL), and olefin 2j (41.6 mg, 0.2 mmol) were reacted for 96 h. Column chromatography (petroleum ether / dichloromethane / diethyl ether = 14 / 10 / 1) gave a highly optically active liquid chiral deuterated compound 12 (74.4 mg, 79%, 95% / 95% D): 97:3 / 98:2er, dr = 1:1 (HPLC conditions: Chiralcel AD-H column, n-hexane / isopropanol = 99.5 / 0.5, 0.5 mL / min, λ = 190 nm, t1 = 41.7 min, t2 = 43.9 min, t3 = 56.2 min, t4 = 61.7 min); [α] D 25=-47.0°(c=0.22,CHCl3); 1 H NMR (400MHz, CDCl3) δ = 7.70-7.26 (m, 30H), 7.20 (t, J = 4.4Hz, 2H), 6.96 (q, J = 4.4Hz, 2H ),6.90(d,J=3.6Hz,1H),6.82(d,J=3.6Hz,1H),4.55(dd,J1=11.6Hz,J2=1.2Hz,0.05H ),4.34(dd,J1=11.4Hz,J2=2.4Hz,0.05H),2.58-2.35(m,4H),2.18-2.10(m,1H),2.01 -1.85(m,2H),1.80(d,J=15.2Hz,1.0H),1.73(d,J=15.2Hz,1.0H),1.60-1.34(m,8H); 13 C NMR(101MHz, CDCl3)δ=170.7,170.4,150.3,147.2,135.83,135.81,134.3,134.2,129.52,129.49,127.83,127 .78,126.9,126.8,124.8,124.0,123.9,123.7,40.4,40.2,36.2,34.4,27.6,26.8,18.3,15.7,14.7; HRMS[M+Na + Calculated value: 492.1534, measured value: 492.1532.

[0123] Example 11

[0124]

[0125] The procedure was similar to Example 1. 4-DPAIPN (1.8 mg, 0.002 mmol), 1a (104.6 mg, 0.4 mmol), chiral thiol S3 (21.6 mg, 0.03 mmol), dry toluene (1.5 mL), deuterated water (0.5 mL), and olefin 2k (50.7 mg, 0.2 mmol) were reacted for 120 h. Column chromatography (petroleum ether / ethyl acetate = 5 / 1) afforded the highly optically active solid chiral deuterated compound 13 (63.6 mg, 62%, 96% D): >99:1 dr (HPLC conditions: Chiralcel AD-H column, n-hexane / isopropanol = 99.3 / 0.7, 0.5 mL / min, λ = 214 nm, t1 (large peak) = 19.5 min, t2 (small peak) = 27.8 min); [α] D 25=-62.5°(c=0.11,CHCl3); mp71-73℃; 1 H NMR (400MHz, CDCl3) δ = 7.92-7.64 (m, 4H), 7.56-7.26 (m, 18H), 4.57 (dd, J1 = 11.4Hz, J2 = 2 .2Hz,0.04H),2.64-2.24(m,3H),2.06(m,1H),1.65(d,J=15.2Hz,1H),1.52-1.30(m,4H); 13 C NMR (101MHz, CDCl3) δ = 171.4, 141.6, 135.8, 134.2, 133.1, 132.1, 129.6, 128.4, 128. 1,127.9,127.4,126.2,126.0,125.3,125.0,41.1,32.0,27.6,25.3,16.4; HRMS[M+Na + Calculated value: 536.2127, measured value: 536.2120.

[0126] Example 12

[0127]

[0128] The procedure was similar to Example 1. (1.6 mg, 0.002 mmol), 1a (104.7 mg, 0.4 mmol), chiral thiol S3 (21.8 mg, 0.03 mmol), dry toluene (1.5 mL), deuterated water (0.5 mL), and olefin 21 (50.6 mg, 0.2 mmol) were reacted for 120 h. Column chromatography (petroleum ether / ethyl acetate = 5 / 1) afforded the highly optically active solid chiral deuterated compound 14 (53.3 mg, 52%, 96% D): >99:1 dr (HPLC conditions: Chiralcel AD-H column, n-hexane / isopropanol = 99.3 / 0.7, 0.5 mL / min, λ = 214 nm, t1 (large peak) = 19.5 min, t2 (small peak) = 27.8 min); [α] D 25 =+16.8°(c=0.20,CHCl3); mp149-150℃; 1H NMR (400MHz, CDCl3) δ=7.86-7.74(m,3H),7.69(s,1H),7.54-7.46(m,2H),7.44-7.32(m,9H),7.31-7.22(m,7H),4.84(d,J=10.8Hz ,0.04H),2.57(t,J=7.2Hz,2H),2.42-2.28(m,1H),1.88-1.78(m,1H),1.74(d,J=15.2Hz,1H),1.57(s,3H),1.22(d,J=15.2Hz,1H); 13 C NMR (100MHz, CDCl3) δ=171.1,142.5,135.8,134.2,133.3,132.1,129.5,128.6,128. 1,127.8,127.4,126.4,126.1,125.1,123.9,41.2,35.1,28.1,17.5,14.7; HRMS[M+Na + Calculated value: 536.2127, measured value: 536.2128.

[0129] Example 13

[0130]

[0131] Procedure: Refer to Example 1. 4-DPAIPN (2.1 mg, 0.002 mmol), 1a (105.2 mg, 0.4 mmol), chiral thiol S3 (21.6 mg, 0.03 mmol), dry toluene (1.5 mL), deuterated water (0.5 mL), and olefin 2m (25.6 mg, 0.2 mmol) were purified by column chromatography (petroleum ether / dichloromethane / diethyl ether = 14 / 10 / 1) to give a highly optically active solid chiral deuterated compound 15 (72.1 mg, 92%, 95% D): 93:7er (HPLC conditions: Chiralcel AD-H column, n-hexane / isopropanol = 98.5 / 1.5, 1.0 mL / min, λ = 214 nm, t1 (large peak) = 10.2 min, t2 (small peak) = 19.5 min); [α] D 25 =-59.1°(c=0.22,CHCl3); mp132-135℃; 1H NMR (400MHz, CDCl3) δ = 7.60-7.50 (m, 6H), 7.47-7.32 (m, 9H), 4.23 (dd, J1 = 11.6Hz, J2 = 1.0Hz, 0 .05H),2.29(s,2H),1.76(d,J=15.2Hz,1H),1.53(t,J=16.0Hz,1H),1.08(s,3H),1.03(s,3H); 13 C NMR (100MHz, CDCl3) δ = 175.8, 135.8, 134.0, 129.7, 127.9, 85.6 (t, J C-D =22.5Hz),44.3,40.3,24.5,21.4,13.4; HRMS[M+Na + Calculated value: 410.1657, measured value: 410.1659.

[0132] Example 14

[0133]

[0134] Procedure Reference Example 1. 4-DPAIPN (1.7 mg, 0.002 mmol), 1a (104.8 mg, 0.4 mmol), chiral thiol S4 (17.0 mg, 0.03 mmol), dry toluene (1.5 mL), deuterated water (0.5 mL), and olefin 2n (19.6 mg, 0.2 mmol) were purified by column chromatography (petroleum ether / ethyl acetate = 5 / 1) to give a highly optically active solid chiral deuterated compound 16 (50.4 mg, 70%, 93% D): 77:23 er (HPLC conditions: Chiralcel AD-H column, n-hexane / isopropanol = 96 / 4, 1.0 mL / min, λ = 214 nm, t1 (minor peak) = 10.2 min, t2 (major peak) = 11.3 min); [α] D 25 =-7.20 (c=0.13, CHCl3); mp83-85℃; 1 H NMR(400MHz, CDCl3)δ=7.72-7.27(m,15H),4.82-4.62(m,0.07H),2.49-2.29(m,2H), 2.21(d,J=14.4Hz,1H),2.02-1.90(m,1H),1.78(d,J=14.4Hz,1H),1.70-1.57(m,1H); 13C NMR (100MHz, CDCl3) δ = 176.8, 135.5, 133.6, 129.9, 128.1, 79.1 (t, J = 23.0Hz), 30.6, 29.5, 21.4; HRMS [M+Na + Calculated value: 382.1344, measured value: 382.1344.

[0135] Example 15

[0136]

[0137] Procedure Reference Example 1. 4-DPAIPN (2.0 mg, 0.002 mmol), 1a (105.0 mg, 0.4 mmol), chiral thiol S5 (17.5 mg, 0.03 mmol), dry toluene (1.5 mL), deuterated water (0.5 mL), and olefin 2n (13.2 mg, 0.14 mmol) were purified by column chromatography (petroleum ether / ethyl acetate = 5 / 1) to give a highly optically active solid chiral deuterated compound ent-16 (34.7 mg, 74%, 94% D): 82:18 er (HPLC conditions: Chiralcel AD-H column, n-hexane / isopropanol = 96 / 4, 1.0 mL / min, λ = 214 nm, t1 (large peak) = 10.2 min, t2 (small peak) = 11.2 min); [α] D 25 =5.53°(c=0.36,CHCl3); mp85-86℃; 1 H NMR (400MHz, CDCl3) δ = 7.64-7.50 (m, 6H), 7.47-7.26 (m, 9H), 4.78-4.67 (m, 0.06H), 2.47-2.29 (m,2H),2.20(d,J=14.4Hz,1H),2.00-1.90(m,1H),1.78(d,J=14.8Hz,1H),1.71-1.57(m,1H); 13 C NMR (100MHz, CDCl3) δ = 176.8, 135.5, 133.6, 129.8, 128.1, 79.0 (t, J = 22.7Hz), 30.6, 29.4, 21.3; HRMS [M+Na + Calculated value: 382.1344, measured value: 382.1343.

[0138] Example 16

[0139]

[0140] Procedure: Refer to Example 1. 4-DPAIPN (1.7 mg, 0.002 mmol), 1a (106.2 mg, 0.4 mmol), chiral thiol S6 (17.7 mg, 0.03 mmol), dry toluene (1.5 mL), deuterated water (0.5 mL), and olefin 2o (29.2 mg, 0.2 mmol) were purified by column chromatography (petroleum ether / ethyl acetate = 5 / 1) to give a highly optically active solid chiral deuterated compound 17 (72.3 mg, 83%, 90% D): 92:8er (HPLC conditions: Chiralcel AD-H column, n-hexane / isopropanol = 96 / 4, 1.0 mL / min, λ = 214 nm, t1 (large peak) = 8.8 min, t2 (small peak) = 14.2 min); [α] D 25 =+2.61(c=0.15,CHCl3); mp110-111℃; 1 H NMR (400MHz, CDCl3) δ=7.73-7.23(m,19H),7.23-7.14(m,1H),4.71-4.51(m,0.1H),3.95 (d,J=9.2Hz,1H),3.62(d,J=8.8Hz,1H),2.05(d,J=14.8Hz,1H),1.61(d,J=14.8Hz,1H); 13 C NMR (100MHz, CDCl3)δ=155.4,136.2,135.4,133.0,130.2,129.2,128.3,125.4,122.7,68.5,17.9; HRMS[M+Na + Calculated value: 459.1610, measured value: 459.1602.

[0141] Example 17

[0142]

[0143] Procedure Reference Example 1. 4-DPAIPN (1.7 mg, 0.002 mmol), 1a (106.2 mg, 0.4 mmol), chiral thiol S5 (17.7 mg, 0.03 mmol), dry toluene (1.5 mL), deuterated water (0.5 mL), and olefin 2p (29.9 mg, 0.2 mmol) were purified by column chromatography (petroleum ether / ethyl acetate = 5 / 1) to give a highly optically active solid chiral deuterated compound 18 (50.8 mg, 61%, 91% D): 82:18 er (HPLC conditions: Chiralcel AD-H column, n-hexane / isopropanol = 96 / 4, 1.0 mL / min, λ = 214 nm, t1 (minor peak) = 9.5 min, t2 (major peak) = 11.6 min); [α] D 25 =-17.3°(c=0.41,CHCl3); mp83-84℃; 1 H NMR (400MHz, CDCl3) δ = 7.67-7.27 (m, 15H), 4.04-3.92 (m, 0.09H), 3.76 (d, J = 8.8Hz, 1H), 3.54-3 .35(m,2H),3.16-3.02(m,1H),2.06(d,J=14.4Hz,1H),1.58-1.18(m,5H),0.91(t,J=7.2Hz,3H); 13 C NMR (100MHz, CDCl3); 157.7, 135.3, 133.2, 130.1, 128.3, 68.7, 52.1 (t, J = 21.8Hz), 40.7, 29.3, 19.9, 17.3, 13.7; HRMS [M+Na + Calculated value: 439.1923, measured value: 439.1921.

[0144] Example 18

[0145]

[0146] Procedure Reference Example 1. 4CzIPN (1.8 mg, 0.002 mmol), 1b (110.9 mg, 0.4 mmol), chiral thiol S3 (21.1 mg, 0.03 mmol), dry toluene (1.5 mL), deuterated water (0.5 mL), and olefin 2a (28.3 mg, 0.2 mmol) were added. Column chromatography (petroleum ether / dichloromethane / diethyl ether = 14 / 10 / 1) afforded the highly optically active solid chiral deuterated compound 19 (69.0 mg, 83%, 95% D): 94:6er (HPLC conditions: Chiralcel AD-H column, n-hexane / isopropanol = 98 / 2, 1.0 mL / min, λ = 214 nm, t1 (minor peak) = 11.4 min, t2 (major peak) = 14.2 min); [α] D 25 =-66.3°(c=0.51,CHCl3); mp83-84℃; 1 H NMR (400MHz, CDCl3) δ=7.64-7.46(m,6H),7.44-7.30(m,6H),7.19(d,J=7.6Hz,2H),4.10(dd,J1=11.6Hz,J 2=2.4Hz,0.05H),2.53-2.30(m,5H),1.76(d,J=14.8Hz,1H),1.64-1.50(m,3H),0.99(s,3H),0.91(s,3H); 13 C NMR (100MHz, CDCl3) δ=170.9,139.4,135.9,135.8,134.77,134.76,130.7,129.4,128.7,127.8,84.2(t,J C-D =22.6Hz),34.0,32.9,27.4,26.5,21.5,19.3,15.0; HRMS[M+Na + Calculated value: 438.1970, measured value: 438.1974.

[0147] Example 19

[0148]

[0149] Procedure: Refer to Example 1. 4CzIPN (4.2 mg, 0.005 mmol), 1c (113.1 mg, 0.4 mmol), chiral thiol S3 (21.1 mg, 0.03 mmol), dry toluene (1.5 mL), deuterated water (0.5 mL), and olefin 2a (28.7 mg, 0.2 mmol) were purified by column chromatography (petroleum ether / dichloromethane / diethyl ether = 14 / 10 / 1) to give a highly optically active solid chiral deuterated compound 20 (71.0 mg, 85%, 96% D): 90:10 er (HPLC conditions: Chiralcel AD-H column, n-hexane / isopropanol = 98 / 2, 1.0 mL / min, λ = 214 nm, t1 (minor peak) = 10.7 min, t2 (major peak) = 12.9 min); [α] D 25 =-61.2°(c=0.50,CHCl3); mp97-99℃; 1 H NMR (400MHz, CDCl3) δ = 7.80-7.30 (m, 12H), 7.07 (t, J = 8.8Hz, 2H), 4.08 (dd, J1 = 11.4Hz, J2 = 2.6Hz, 0 .04H),2.60-2.20(m,2H),1.77(d,J=14.8Hz,1H),1.65-1.48(m,3H),1.11-0.79(d,J=33.2Hz,6H); 13 C NMR (100MHz, CDCl3) δ = 170.9, 165.2, 162.7, 138.0 (d, J C-F =7.5Hz),135.8(d,J C-F =7.0Hz),134.5,134.2,129.9(d,J C-F =3.7Hz),129.6(d,J C-F =1.7Hz),127.9,115.1(d,J C-F =19.6Hz),34.0,32.9,27.4,26.5,19.2,15.0; 19 F NMR (376MHz, CDCl3) δ = -111.1; HRMS [M+Na + Calculated value: 442.1719, measured value: 442.1714.

[0150] Example 20

[0151]

[0152] Procedure: Refer to Example 1. 4-DPAIPN (2.0 mg, 0.002 mmol), 1d (100.9 mg, 0.4 mmol), chiral thiol S3 (21.1 mg, 0.03 mmol), dry toluene (1.5 mL), deuterated water (0.5 mL), and olefin 2a (28.0 mg, 0.2 mmol) were purified by column chromatography (petroleum ether / dichloromethane / diethyl ether = 14 / 10 / 1) to give a highly optically active solid chiral deuterated compound 21 (64.6 mg, 83%, 97% D): 95:5er (HPLC conditions: Chiralcel AD-H column, n-hexane / isopropanol = 98.7 / 1.3, 1.0 mL / min, λ = 214 nm, t1 (minor peak) = 17.0 min, t2 (major peak) = 18.5 min); [α] D 25 =-68.0°(c=0.50,CHCl3); mp81-87℃; 1 H NMR (400MHz, CDCl3) δ=7.75(d,J=1.6Hz,1H),7.67-7.58(m,4H),7.46-7.32(m,6H),6.83(d,J=3.6Hz,1H),6.45(dd,J1=6.4Hz,J2=1.6H z,1H),4.15(dd,J1=11.2Hz,J2=2.4Hz,0.03H),2.56-2.30(m,2H),1.71(d,J=15.2Hz,1H),1.65-1.54(m,3H),0.99(s,3H),0.93(s,3H); 13 C NMR (100MHz, CDCl3) δ = 171.0, 155.1, 147.8, 135.6, 135.5, 133.4, 133.3, 129.8, 127.90, 127.86, 124.1, 109.8, 84.0 (t, J C-D =22.2Hz),33.9,32.9,27.4,26.4,19.3,14.8; HRMS[M+Na + Calculated value: 414.1606, measured value: 414.1607.

[0153] Example 21

[0154]

[0155] The operation was carried out in accordance with Example 1. 4-DPAIPN (2.1 mg, 0.002 mmol), 1e (186.3 mg, 0.4 mmol), chiral thiol S3 (22.1 mg, 0.03 mmol), dry toluene (1.5 mL), deuterated water (0.5 mL), olefin 2a (28.1 mg, 0.2 mmol). Column chromatography (petroleum ether / dichloromethane / diethyl ether = 14 / 10 / 1) gave a highly optically active liquid chiral deuterated compound 22 (105.6 mg, 87%, 95% D): 95:5 / 94:6 er, dr = 1:1 (HPLC conditions: Chiralcel AD-H column, n-hexane / isopropanol = 90 / 10, 0.5 mL / min, λ = 214 nm, t1 = 25.7 min, t2 = 28.9 min, t3 = 30.3 min, t4 = 34.3 min); [α] D 25 =-39.2°(c=0.26,CHCl3); 1 H NMR(400MHz, CDCl3)δ=7.65-7.47(m,6H),7.46-7.32(m,6H),7.29(d,J=8.0H z,2H),7.13(d,J=8.0Hz,2H),7.01(d,J=8.4Hz,2H),4.07(dd,J1=11.6Hz,J2 =2.0Hz,0.05H),3.93(q,J=7.2Hz,1H),2.56-2.24(m,4H),1.93-1.80(m,1H) ,1.75(d,J=14.8Hz,1H),1.65-1.44(m,6H),0.99(s,3H),0.94-0.76(m,9H); 13 CNMR(100MHz, CDCl3)δ=173.1,170.9,152.1,140.8,137.2,137.1,135.8,134.29,134.27,131.8,129.6,129.5,127.9,127.1,120.9,84.2(t,J C-D =22.2 Hz), 45.2, 45.0, 33.9, 32.9, 30.1, 27.4, 26.5, 22.4, 19.2, 18.4, 14.9; HRMS [M+Na+] calcd: 628.2964, found: 628.2957.

[0156] Example 22

[0157]

[0158] Procedure: Refer to Example 1. 4-DPAIPN (1.8 mg, 0.002 mmol), 1f (179.1 mg, 0.4 mmol), chiral thiol S3 (22.1 mg, 0.03 mmol), dry toluene (1.5 mL), deuterated water (0.5 mL), and olefin 2a (29.0 mg, 0.2 mmol) were purified by column chromatography (petroleum ether / dichloromethane / diethyl ether = 14 / 10 / 1) to give a highly optically active liquid chiral deuterated compound 23 (78.5 mg, 67%, 97% D): 95:5 dr (HPLC conditions: Chiralcel AD-H column, n-hexane / isopropanol = 95 / 5, 1 mL / min, λ = 214 nm, t1 (minor peak) = 10.3 min, t2 (major peak) = 14.3 min); [α] D 25 =-39.2°(c=0.26,CHCl3); 1 H NMR(400MHz, CDCl3)δ=7.65-7.47(m,6H),7.46-7.32(m,6H),7.29(d,J=8.0H z,2H),7.13(d,J=8.0Hz,2H),7.01(d,J=8.4Hz,2H),4.07(dd,J1=11.6Hz,J2 =2.0Hz,0.05H),3.93(q,J=7.2Hz,1H),2.56-2.24(m,4H),1.93-1.80(m,1H) ,1.75(d,J=14.8Hz,1H),1.65-1.44(m,6H),0.99(s,3H),0.94-0.76(m,9H); 13 C NMR (100MHz, CDCl3) δ=173.1,170.9,152.1,140.8,137.2,137.1,135.8,134.29,134.27,131.8,129.6,129.5,127.9,127.1,120.9,84.2(t,J C-D =22.2 Hz), 45.2, 45.0, 33.9, 32.9, 30.1, 27.4, 26.5, 22.4, 19.2, 18.4, 14.9; HRMS [M+Na+] calcd: 628.2964, found: 628.2957.

[0159] Example 23

[0160]

[0161] Procedure Reference Example 1. 4-DPAIPN (1.5 mg, 0.002 mmol), 1 g (40.6 mg, 0.2 mmol), chiral thiol S3 (21.7 mg, 0.03 mmol), dry toluene (1.5 mL), deuterated water (0.5 mL), and olefin 2q (33.8 mg, 0.24 mmol) were added. Column chromatography (dichloromethane / methanol = 30 / 1) afforded the highly optically active solid chiral deuterated compound 23 (42.9 mg, 72%, 93% D): 96:4er (HPLC conditions: Chiralcel AD-H column, n-hexane / isopropanol = 65 / 35, 0.5 mL / min, λ = 214 nm, t1 (large peak) = 14.0 min, t2 (small peak) = 15.1 min); [α] D 25 =-80.6°(c=0.21,CHCl3); mp172-173℃; 1 H NMR(400MHz, CDCl3)δ=7.87-7.65(m,4H),7.64-7.45(m,6H),7.34(brs,1H),3.3 7(t,J=11.2Hz,0.07H),2.44-2.09(m,4H),1.64-1.49(m,2H),1.02-0.84(m,6H); 13 C NMR (100MHz, CDCl3) δ = 170.6, 133.1 (d, J C-P =99.9Hz),132.24(d,J C-P =2.6Hz),132.19(d,J C-P =2.8Hz),131.1(d,J C-P =9.0Hz),130.4(d,J C-P =98.1Hz),130.3(d,J C-P =9.6Hz),128.9(d,J C-P =7.4Hz),128.8(d,J C-P =7.6Hz),34.9,32.0(d,J C-P =11.6Hz),30.1(d,J C-P =70.1Hz),28.2,26.7,18.6; 31 P NMR (162MHz, CDCl3) δ = 33.4; HRMS [M+Na + Calculated value: 365.1500, measured value: 365.1497.

[0162] Example 24

[0163]

[0164] Procedure: Refer to Example 1. 4-DPAIPN (1.9 mg, 0.002 mmol), 1h (42.8 mg, 0.2 mmol), chiral thiol S3 (21.6 mg, 0.03 mmol), dry toluene (1.5 mL), deuterated water (0.5 mL), and olefin 2a (33.0 mg, 0.24 mmol) were added. Column chromatography (petroleum ether / ethyl acetate = 5 / 1) afforded the highly optically active solid chiral deuterated compound 23 (57.0 mg, 80%, 81% D): 88:12 er (HPLC conditions: Chiralcel AD-H column, n-hexane / isopropanol = 60 / 40, 0.5 mL / min, λ = 214 nm, t1 (large peak) = 19.0 min, t2 (small peak) = 24.9 min); [α] D 25 =-83.1°(c=0.24,CHCl3); mp151-153℃; 1 H NMR (400MHz, CDCl3) δ = 8.04-7.76 (m, 4H), 7.62-7.33 (m, 6H), 4.81 (dd, J1 = 15.4Hz, J2 = 9.0Hz, 0.19 H),3.06-2.76(m,1H),2.57-2.24(m,3H),1.86-1.73(m,1H),1.66-1.54(m,1H),1.09-0.87(m,6H); 13 C NMR (100MHz, CDCl3) δ = 170.1, 133.9 (d, J C-P =82.8Hz),131.8(d,J C-P =10.7Hz),131.6(d,J C-P =3.1Hz),131.5(d,J C-P =2.9Hz),131.4,130.7(d,J C-P =10.0Hz),128.7(d,J C-P =12.1Hz),128.2(d,J C-P =12.6Hz),81.0-80.4(m),34.1(d,J C-P =55.9Hz),34.0,32.4(d,J C-P =10.1Hz),27.2,26.2,19.8; 31 P NMR (162MHz, CDCl3) δ = 42.6; HRMS [M+H + Calculated value: 360.1292, measured value: 360.1291.

[0165] Example 25

[0166]

[0167] Procedure: Refer to Example 1. 4-DPAIPN (1.5 mg, 0.002 mmol), 1i (30.5 mg, 0.2 mmol), chiral thiol S3 (22.2 mg, 0.03 mmol), dry toluene (1.5 mL), deuterated water (0.5 mL), and olefin 2o (65.0 mg, 0.24 mmol) were purified by column chromatography (petroleum ether / ethyl acetate = 5 / 1) to give a highly optically active solid chiral deuterated compound 23 (51.9 mg, 62%, 97% D): 96:4er (HPLC conditions: Chiralcel IC-H column, n-hexane / isopropanol = 80 / 20, 0.5 mL / min, λ = 214 nm, t1 (minor peak) = 15.6 min, t2 (major peak) = 17.8 min); [α] D 25 =-195.4°(c=0.25,CHCl3); mp78-79℃; 1 H NMR(400MHz, CDCl3)δ=7.41-7.19(m,8H),7.17-7.09(m,2H),5.85-5.75(m,0.03H),4.27-3.90(m,4H), 2.76-2.50(m,3H),2.34-2.15(m,2H),1.86-1.70(m,1H),1.29(t,J=7.0Hz,3H),1.24(t,J=7.2Hz,3H); 13 C NMR (100MHz, CDCl3) δ = 168.7, 143.2 (d, J C-P =15.4Hz),128.9(d,J C-P =8.2Hz),127.3(d,J C-P =28.7Hz),127.1(d,J C-P =26.0Hz),63.7(d,J C-P =6.3Hz),61.9(d,J C-P =6.4Hz),48.0(d,J C-P =13.9Hz),37.8(d,J C-P =112.9Hz),27.5(d,J C-P =24.0Hz),16.2(d,J C-P =7.1Hz),16.0(d,J C-P =7.5Hz); 31P NMR (162MHz, CDCl3) δ = 94.9; HRMS [M+Na + Calculated value: 442.1323, measured value: 442.1320.

[0168] Example 26

[0169]

[0170] Procedure Reference Example 1. 4-DPAIPN (1.5 mg, 0.002 mmol), 1j (56.0 mg, 0.2 mmol), chiral thiol S3 (21.6 mg, 0.03 mmol), dry toluene (1.5 mL), deuterated water (0.5 mL), and olefin 2o (37.0 mg, 0.24 mmol) were purified by column chromatography (petroleum ether / ethyl acetate = 2 / 1) to give a highly optically active solid chiral deuterated compound 27 (42.3 mg, 67%, 88% D): 94:6er (HPLC conditions: Chiralcel AD-H column, n-hexane / isopropanol = 70 / 30, 0.8 mL / min, λ = 214 nm, t1 (large peak) = 6.1 min, t2 (small peak) = 8.1 min); [α] D 25 =-32.4°(c=0.17,CHCl3); mp117-119℃; 1 H NMR (400MHz, CDCl3) δ=7.88-7.75(m,2H),7.75-7.62(m,2H),7.57-7.33(m,6H),4.55-4.43(m,0.12H),2.70- 2.57(m,1H),2.54-2.36(m,2H),2.29-2.18(m,1H),1.79-1.68(m,1H),1.65-1.54(m,1H),1.50-0.55(m,9H); 13 C NMR (100MHz, CDCl3) δ = 170.1, 132.9 (d, J C-P =9.8Hz),131.9(d,J C-P =9.1Hz),131.5(d,J C-P =2.5Hz),131.2(d,J C-P =2.5Hz),130.0(d,J C-P =57.4Hz),128.3(d,J C-P =9.9Hz),128.5(d,J C-P =10.4Hz),127.5(d,J C-P =55.0Hz),81.4(t,JC-P =23.4Hz),33.9,32.6(d,J C-P =8.8Hz),27.6(d,J C-P =36.5Hz),27.2,26.2,19.4; 31 P NMR (162MHz, CDCl3) δ = 16.2 (d, J = 77.8Hz); 11 B NMR (128MHz, CDCl3) δ = -39.4; HRMS [M+Na + Calculated value: 364.1718, measured value: 364.1726.

[0171] Example 27

[0172]

[0173] To a dry reaction flask, Hanqi ester (HE, 63.2 mg, 0.25 mmol), 1k (68.0 mg, 0.2 mmol), S3 (10.9 mg, 0.015 mmol), (PhO)2PO2H (4.9 mg, 0.02 mmol), and 4DPAIPN (1.8 mg, 0.002 mmol) were added sequentially. The flask was then transferred to a glove box, followed by the addition of dry toluene (0.75 mL), deuterated water (0.25 mL), and olefin 2a (14.2 mg, 0.1 mmol). The reaction system was then sealed, removed from the glove box, and allowed to react at 10°C under blue light for 36 h. After the reaction, 5 mL of water and 5 mL of dichloromethane were added to the system, the organic layer was separated, and the aqueous layer was extracted with dichloromethane (5 mL × 3). The organic layers were combined, washed with saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography (petroleum ether / ethyl acetate = 5 / 1) to obtain a liquid chiral deuterated compound 28 (28.1 mg, 71%, 94% D) with high optical activity: 93:7er (HPLC conditions: Chiralcel AD-H column, n-hexane / isopropanol = 90 / 10, 0.5 mL / min, λ = 214 nm, t1 (small peak) = 10.0 min, t2 (large peak) = 10.9 min); [α] D 25 =-44.8°(c=0.16,CHCl3); 1H NMR (400MHz, CDCl3) δ = 4.43 (dd, J1 = 9.2Hz, J2 = 1.2Hz, 0.06H), 4.02 (tt, J1 = 11.6Hz, J2 = 3.5Hz, 1H),3.01(tt,J1=11.8Hz,J2=3.8Hz,1H),2.66-2.26(m,6H),1.91-1.02(m,23H),0.99(s,3H); 13 C NMR (100MHz, CDCl3) δ = 170.8, 162.0 (t, J = 27.1Hz), 118.9 (t, J = 257.1Hz), 81.0 (t, J = 2.8Hz), 57.1, 36.3-35.6 ( m),34.11,34.08,31.9,31.8,30.9,29.0,28.9,27.1,26.4,26.3,26.23,26.20,25.6,25.5,25.22,25.17,19.3; 19 F NMR (376MHz, CDCl3) δ = -97.8 (d, J = 279.4Hz), -100.4 (d, J = 279.0Hz); HRMS [M + Na + Calculated value: 423.2540, measured value: 423.2537.

[0174] Example 28

[0175]

[0176] Procedure Reference Example 27: HE (63.4 mg, 0.25 mmol), 11 (51.8 mg, 0.2 mmol), S3 (10.9 mg, 0.015 mmol), (PhO)2PO2H (5.1 mg, 0.02 mmol), toluene (0.75 mL), 2a (14.4 mg, 0.1 mmol), and deuterated water (0.25 mL). Column chromatography (petroleum ether / ethyl acetate = 5 / 1) afforded the highly optically active chiral deuterated compound 28 (25.6 mg, 78%, 92% D) in a 92:8 ratio (HPLC conditions: Chiralcel OD-H column, n-hexane / isopropanol = 90 / 10, 0.5 mL / min, λ = 214 nm, t1 (large peak) = 10.6 min, t2 (small peak) = 11.4 min); [α] D 25 =-40.1°(c=0.18,CHCl3); 1H NMR (400MHz, CDCl3) δ = 4.56-4.40 (m, 1.08H), 3.56-3.42 (m, 1H), 2.66-2.44 (m, 3H), 2.44-2.27 (m, 1H), 1.86-1.74(m,1H),1.73-1.61(m,1H),1.45-1.37(m,6H),1.26-1.18(m,6H),1.05(s,3H),0.99(s,3H); 13 C NMR (100MHz, CDCl3) δ = 170.7, 161.7 (t, J = 27.3Hz), 118.7 (t, J = 255.6Hz), 48.4 (t, J = 7. 5Hz), 46.9, 35.9 (t, J = 22.9Hz), 34.1, 31.8, 27.1, 26.2, 20.5, 20.4, 19.81, 19.78, 19.3; 19 F NMR (376MHz, CDCl3) δ = -97.8 (d, J = 279.4Hz), -100.6 (d, J = 279.4Hz); HRMS (ESI) [M+Na + Calculated value: 343.1914, measured value: 343.1914.

[0177] Example 29

[0178]

[0179] Procedure Reference Example 27. HE (63.3 mg, 0.25 mmol), 1m (67.5 mg, 0.2 mmol), S3 (10.8 mg, 0.015 mmol), (PhO)2PO2H (5.0 mg, 0.02 mmol), toluene (0.75 mL), 2m (13.0 mg, 0.1 mmol), and deuterated water (0.25 mL) were added. Column chromatography (petroleum ether / ethyl acetate = 5 / 1) afforded a highly optically active liquid chiral deuterated compound 30 (27.0 mg, 70%, 91% D): 96:4er (HPLC conditions: Chiralcel AD-H column, n-hexane / isopropanol = 90 / 10, 0.5 mL / min, λ = 214 nm, t1 (large peak) = 9.4 min, t2 (small peak) = 10.4 min); [α] D 25 =-40.6°(c=0.18,CHCl3); 1H NMR (400MHz, CDCl3) δ = 4.44 (dd, J1 = 9.6Hz, J2 = 1.6Hz, 0.09H), 4.03 (tt, J1 = 11.7Hz, J2 = 3.5Hz,1H),3.02(tt,J1=12.0Hz,J2=3.8Hz,1H),2.66-2.25(m,6H),1.99-0.99(m,24H); 13 C NMR (100MHz, CDCl3) δ = 175.5, 161.7 (t, J = 27.0Hz), 118.70 (t, J = 257.4Hz), 81.4 (t, J = 23.1Hz), 57.2-57.0 (m) ,44.1,39.7,39.6,34.7-34.2(m),30.8,28.9,26.27,26.25,25.51,25.47,25.14,25.09,24.14,24.11,21.0; 19 F NMR (376MHz, CDCl3) δ = -97.0 (d, J = 281.6Hz), -100.7 (d, J = 281.6Hz); HRMS (ESI) calcd forC 21 H 32 DF2NNaO3[M+Na + ]:409.2383,found:409.2387.

[0180] Example 30

[0181]

[0182] Under nitrogen, lithium aluminum hydride (10.3 mg, 0.25 mmol, 96% D, 96:4er) and 4 mL of diethyl ether were added sequentially to a dry reaction tube. A solution of chiral deuterated compound 3 (40.1 mg, 0.1 mmol) in diethyl ether was then added dropwise at 0°C. After the addition was complete, the mixture was warmed to room temperature and refluxed for 4 h. After cooling to room temperature, water (0.1 mL) was added to the reaction tube, followed by 3 M NaOH (0.3 ml). The mixture was stirred for 10 minutes, and then water (0.3 mL) was added. The mixture was filtered, and the organic layer was separated. The aqueous layer was extracted with dichloromethane (10 mL × 3). The organic layers were combined, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography (petroleum ether / diethyl ether = 5 / 1) to give solid compound 31 (34.4 mg, 85%, 93% D): 96:4er (HPLC determination conditions: Chiralcel OD-H column, n-hexane / isopropanol = 95 / 5, 1.0 mL / min, λ = 214 nm, t R (big peak)=6.8min,t R (small peak) = 8.3 min); [α]D 25 =-17.5°(c=0.20,CHCl3); mp100-102℃; 1 H NMR (400MHz, CDCl3) δ=7.71-7.48(m,6H),7.45-7.22(m,9H),3.66(dd,J1=9.2H z,J2=4.4Hz,0.06H),3.59-3.37(m,2H),1.80-1.16(m,8H),1.01-0.73(m,6H); 13 C NMR (100MHz, CDCl3) δ = 135.7, 135.1, 129.4, 127.8, 74.6 (t, J C-D =20.8Hz),63.3,38.0,34.2,26.8,22.7,22.2,16.1; HRMS[M+Na + Calculated value: 428.2127, measured value: 428.2132.

[0183] To a solution of 31 (40.7 mg, 0.1 mmol, 93% D, 96:4 er) in dichloromethane (1 mL) was added triethylamine (45.0 μL, 0.3 mmol) and benzoyl chloride (15.0 μL, 0.11 mmol) dropwise at 0°C and allowed to react at room temperature for 10 h. After completion of the reaction, dichloromethane (10 mL) and water (10 mL) were added, and the organic layer was separated. The aqueous layer was extracted with dichloromethane (10 mL x 3). The combined organic layers were dried over anhydrous sodium sulfate, and concentrated to obtain the crude product, which was purified by flash column chromatography (petroleum ether / ethyl acetate = 10 / 1) to afford the benzoyl-protected intermediate. Under nitrogen protection, a tetrahydrofuran (1 mL) solution of the intermediate was added to a dry reaction tube, followed by a tetrahydrofuran solution of tetrabutylammonium fluoride (1 M, 1.6 mL, 1.6 mmol), and the reaction was carried out at room temperature for 10 h. Methanol (1 mL), potassium bicarbonate (80.3 mg, 0.8 mmol), and 30% hydrogen peroxide (0.8 mL, 2.0 mmol) were then added to the reaction system in sequence, and the reaction was continued for 10 h. After the reaction, saturated sodium bicarbonate solution was added to the reaction system, the organic phase was separated, and the aqueous layer was extracted with diethyl ether (10 mL × 3). The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography (petroleum ether / diethyl ether = 5 / 1) to give liquid compound 32 (31.1 mg, 51%, 93% D, over 3 steps), 95:5er (HPLC determination conditions: Chiralcel AD-H column, n-hexane / isopropanol = 97 / 3, 0.5 mL / min, λ = 214 nm, t R (big peak)=46.6min,tR (small peak) = 52.8 min); [α] D 25 =-16.3°(c=0.14,CHCl3); 1 H NMR (400MHz, CDCl3) δ=8.16-7.94(m,2H),7.60-7.50(m,1H),7.48-7.34(m,2H),4.30(t,J=6.8Hz,2 H),3.58(q,J=6.4Hz,0.07H),1.87-1.66(m,2H),1.51-1.32(m,2H),1.14(s,3H),0.96-0.79(m,6H); 13 C NMR (100MHz, CDCl3) δ = 166.7, 132.8, 130.4, 129.5, 128.3, 73.7 (t, J C-D =21.4Hz),65.8,37.0,34.7,23.4,22.6,22.3,17.6; HRMS[M+Na + Calculated value: 274.1524, measured value: 274.1524.

[0184] Example 31

[0185]

[0186] Under nitrogen protection and 0°C, potassium tert-butoxide (68.2 mg, 0.6 mmol), tetrahydrofuran (2 mL), and tert-butyl peroxide (70% in water, 79.3 mg, 0.6 mmol) were added sequentially to a dry reaction tube. The mixture was stirred for 10 minutes. Subsequently, a tetrahydrofuran solution of compound 17 (87.4 mg, 0.2 mmol, 90% D, 92:8er) and tetrabutylammonium fluoride (1.0 M in THF, 0.6 mL, 0.6 mmol) were added in sequence, and the reaction was continued at 70°C for 12 hours. After the reaction was completed, water (10 mL) and diethyl ether (10 mL) were added, the organic layer was separated, and the aqueous layer was extracted with diethyl ether (10 mL × 3). The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography (petroleum ether / diethyl ether = 5 / 1) to give liquid compound 33 (16.8 mg, 47%, 90% D), 91:9er (HPLC determination conditions: Chiralcel AD-H column, n-hexane / isopropanol = 90 / 10, 1.0 mL / min, λ = 214 nm, t R (big peak)=6.8min,t R (small peak) = 8.3 min); [α] D 25=-53.8°(c=0.11,CHCl3); 1 H NMR (400MHz, CDCl3) δ = 7.46-7.34 (m, 4H), 7.23-7.15 (m, 1H), 4.47-4.63 (m, 2.10H), 4.02 (d, J = 8.4Hz, 1H), 1.33 (s, 3H); 13 C NMR (100MHz, CDCl3) δ = 155.7, 136.5, 129.1, 125.2, 122.0, 121.9, 68.5, 51.9 (t, J C-D =22.0Hz), 18.3; HRMS [M+Na + Calculated: 201.0745, predicted: 201.0744. (Reference: Chen, J., Cheng, B., Cao M., Lu, Z. Angew. Chem. Int. Ed, 2015, 54, 4661-4664.)

[0187] Example 32

[0188]

[0189] Under nitrogen, 17 (43.7 mg, 0.1 mmol, 90% D, 92:8 ratio), dichloromethane (1 mL), and BF3·2AcOH (140 μL, 1 mmol) were added sequentially to a dry reaction tube, and the mixture was refluxed for 5 h. After cooling to room temperature, saturated sodium bicarbonate solution and ethyl acetate (10 mL) were added to the mixture. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate (5 mL x 3). The combined organic layers were dried over anhydrous sodium sulfate, and concentrated to obtain the intermediate without column chromatography. Tetrahydrofuran / methanol (v / v = 1 / 1, 1.2 mL) was then added directly to the intermediate as solvent, followed by potassium fluoride (17.9 mg, 0.3 mmol), potassium bicarbonate (10.5 mg, 0.1 mmol), and 30% hydrogen peroxide (120 μL, 1 mmol), and the mixture was refluxed for 12 h. After the reaction, saturated sodium bicarbonate solution and ethyl acetate (10 mL) were added to the mixture, the organic layer was separated, and the aqueous layer was extracted with ethyl acetate (10 mL × 3). The organic layers were combined, washed with saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography (petroleum ether / diethyl ether = 1 / 1) to give solid compound 34 (11.7 mg, 60%, 90% D), 91:9er (HPLC determination conditions: Chiralcel OD-H column, n-hexane / isopropanol = 80 / 20, 1.0 mL / min, λ = 214 nm, t R (big peak)=18.1min,t R(small peak) = 20.6 min); [α] D 25 =-40.0°(c=0.15,CHCl3); mp111-113℃; 1 H NMR (400MHz, CD3OD) δ = 7.57-7.46 (m, 2H), 7.45-7.34 (m, 2H), 7.27-7.16 (m, 1H), 4.66-4 .49(m,1.10H),4.43(d,J=8.4Hz,1H)),3.66(d,J=12.0Hz,1H)),3.55(d,J=12.0Hz,1H); 13 C NMR (100MHz, CD3OD) δ = 158.7, 137.9, 130.1, 126.7, 124.0, 66.0, 60.3, 59.0 (t, J C-D =22.1 Hz); HRMS [M+Na + Calculated: 217.0696, found: 217.0694. (Reference: El-Sepelgy, O., Haseloff, S., Alamsetti, S., Schneider, K.C. Angew. Chem. Int. Ed. 2014, 53, 7923-7927.)

[0190] Example 33

[0191]

[0192] Compound 17 (43.7 mg, 0.1 mmol, 90% D, 92:8 er), sodium hydroxide (41.2 mg, 1 mmol), and ethanol (1 mL) were added sequentially to a dry reaction tube. The mixture was then refluxed for 5 h. After the reaction, 10 mL of water and 10 mL of dichloromethane were added, the organic layer was separated, and the aqueous layer was extracted with dichloromethane (10 mL × 3). The organic layers were combined, washed with saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography (petroleum ether / diethyl ether = 5 / 1) (31.8 mg, 77%, 90% D) to obtain liquid compound 35:92:8 er (HPLC conditions: Chiralcel OD-H column, n-hexane / isopropanol = 80 / 20, 1 mL / min, λ = 214 nm, t R (small peak) = 9.3min,t R (big peak) = 14.3min); [α] D 25 =9.3 (c = 0.23, CHCl3); 1H NMR (400MHz, CDCl3) δ=7.55-7.44(m,6H),7.43-7.24(m,9H),7.06(t,J=8.0Hz,2H),6.69(t,J=7.4Hz,1H),6.29(d,J=7 .6Hz,2H),3.73-3.66(m,0.1H),3.61(d,J=11.2Hz,1H)),3.43(d,J=10.8Hz,1H),3.31-2.42(m,2H),1.87-1.16(m,2H); 13 C NMR (100MHz, CDCl3) δ=145.9,135.6,134.3,129.6,129.2,128.0,118.3,114.1,65.8,16.7; HRMS[M+Na + Calculated value: 424.1814, measured value: 424.1818.

[0193] All documents mentioned in this application are incorporated herein by reference, just as if each document were incorporated herein by reference individually. It should also be understood that after reading the above teachings of the present invention, those skilled in the art may make various changes or modifications to the present invention, and that such equivalents also fall within the scope of the claims appended hereto.

Claims

1. A method for preparing an optically active deuterated compound, wherein the deuterated compound has the structural formula shown in Formula I below: in, R 1 for R 2 and R 3 Each is independently selected from the following group: H, substituted or unsubstituted C1-C5 straight or branched alkyl, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted 5-7 membered heteroaryl, or R 2 and R 3 and the carbon atoms to which they are connected together form a 4-8 membered saturated carbocyclic or heterocyclic ring; Y is selected from the group consisting of O, CH2; Z is selected from the following group: NR, O; n is 0 or 1; R 4 and R 5 Each is independently selected from the group consisting of: substituted or unsubstituted phenyl; R 6 Selected from the following group: substituted or unsubstituted phenyl, substituted or unsubstituted 5-7 membered heteroaryl; wherein, the R 6 Substitution means that one or more hydrogen atoms are replaced by a substituent selected from the group consisting of halogen, amino, hydroxy, nitro, cyano, trifluoromethyl, C1-C 12 Alkyl or cycloalkyl, C1-C 12 Alkoxy, unsubstituted or C 1-4 Alkylamino-substituted C1-C 12 Alkylamino, C2-C6 ester, C2-C6 acyl, C2-C6 amide, thio C1-C 12 Alkyl, carboxyl, C5-C 12 Aryl, C5-C 12 Heterocyclic group, or said R 6 Optionally includes 1 substituent R selected from the group consisting of 7 C(O)O-; the R 7 Selected from the group consisting of substituted or unsubstituted phenyl, substituted or unsubstituted 5-7 membered heteroaryl, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted benzyl; R is selected from the following group: H, substituted or unsubstituted C1-C5 straight or branched alkyl, substituted or unsubstituted phenyl; In the formula, the configuration of the chiral deuterated center marked with * is R or S; The substitution refers to the substitution of one or more hydrogen atoms on the group by a substituent selected from the group consisting of halogen, amino, hydroxy, nitro, cyano, trifluoromethyl, C1-C 12 Alkyl or cycloalkyl, C1-C 12 Alkoxy, oxygen atom, unsubstituted or replaced by C 1-4 Alkylamino-substituted C1-C 12 Alkylamino, C2-C6 ester, C2-C6 acyl, C2-C6 amide, thio C1-C 12 Alkyl, carboxyl, C5-C 12 Aryl, C5-C 12 heterocyclic group; wherein the heterocyclic group contains 1-5 heteroatoms selected from N, O or S; Characterized in that the method comprises the steps of: Under blue light irradiation, in an organic solvent and deuterated water mixture, a photocatalyst and a chiral thiol are used to synergistically catalyze the reaction of compound 1 and compound 2 to obtain a compound of formula I; wherein X is selected from the group consisting of: H; The chiral thiol is selected from S3, S4, S5 or S6: The photocatalyst is selected from the group consisting of 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile (4CzIPN), 2,4,5,6-tetrakis(diphenylamino)isophthalonitrile (4DPAIPN); The organic solvent is selected from the group consisting of benzene, toluene, tetrahydrofuran, p-xylene, o-xylene, m-xylene, mesitylene, or a combination thereof.

2. A method for preparing an optically active deuterated compound, wherein the deuterated compound has the structural formula shown in Formula I below: in, R 1 for R 2 and R 3 Each is independently selected from the following group: H, substituted or unsubstituted C1-C5 straight or branched alkyl, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted 5-7 membered heteroaryl, or R 2 and R 3 and the carbon atoms to which they are connected together form a 4-8 membered saturated carbocyclic or heterocyclic ring; M is selected from the group consisting of P(O), P(S), and P→(BH3); Y is selected from the group consisting of O, CH2; Z is selected from the following group: NR, O; n is 0 or 1; R 4 and R 5 Each is independently selected from the following group: substituted or unsubstituted C1-C5 straight or branched alkoxy, substituted or unsubstituted phenyl; R is selected from the following group: H, substituted or unsubstituted C1-C5 straight or branched alkyl, substituted or unsubstituted phenyl; In the formula, the configuration of the chiral deuterated center marked with * is R or S; The substitution refers to the substitution of one or more hydrogen atoms on the group by a substituent selected from the group consisting of halogen, amino, hydroxy, nitro, cyano, trifluoromethyl, C1-C 12 Alkyl or cycloalkyl, C1-C 12 Alkoxy, oxygen atom, unsubstituted or replaced by C 1-4 Alkylamino-substituted C1-C 12 Alkylamino, C2-C6 ester, C2-C6 acyl, C2-C6 amide, thio C1-C 12 Alkyl, carboxyl, C5-C 12 Aryl, C5-C 12 heterocyclic group; wherein the heterocyclic group contains 1-5 heteroatoms selected from N, O or S; Characterized in that the method comprises the steps of: Under blue light irradiation, in an organic solvent and deuterated water mixture, a photocatalyst and a chiral thiol are used to synergistically catalyze the reaction of compound 1 and compound 2 to obtain a compound of formula I; wherein X is selected from the group consisting of: H; The chiral thiol is selected from S3, S4, S5 or S6: The photocatalyst is selected from the group consisting of 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile (4CzIPN), 2,4,5,6-tetrakis(diphenylamino)isophthalonitrile (4DPAIPN); The organic solvent is selected from the group consisting of benzene, toluene, tetrahydrofuran, p-xylene, o-xylene, m-xylene, mesitylene, or a combination thereof.

3. The method according to claim 1 or 2, wherein: In the reaction, the wavelength of the blue light is in the range of 450-455 nm.

4. The method according to claim 1 or 2, wherein: In the reaction, the organic solvent is toluene.

5. The method according to claim 1 or 2, wherein: In the reaction, the molar ratio of compound 1:compound 2 is 1 to 3:

1.

6. The method according to claim 1 or 2, wherein: In the reaction, the molar ratio of photocatalyst to compound 2 is 0.1 to 1:1; and / or The molar ratio of chiral thiol: compound 2 is 0.1 to 1:

1.

7. The method according to claim 1 or 2, wherein: In the reaction, the volume ratio of the organic solvent to the deuterated water is 1:1 to 5:

1.

8. A method for preparing a compound of formula II, characterized in that: The method comprises the steps of: The deuterated compound of formula I is prepared by the method according to any one of claims 1 to 7, and In an organic solvent, in the presence of a base, the compound of formula I is subjected to ring opening to obtain the compound of formula II.

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