A synthetic method for preparing chiral amines by manganese-catalyzed asymmetric hydrogenation of N-tert-butylsulfonylimide.

Abstract

This invention provides a method for preparing chiral N-tert-butylsulfonamide compounds. The method uses N-tert-butylsulfonylimide as a starting material, employs Mn(CO)₅Br and a chiral PNN ligand as catalysts, and an alcohol as a solvent. A hydrogenation reaction occurs in this homogeneous catalytic system, yielding axially chiral diaryl nitrophenol compounds in high yield (99%) and with high ee values ​​(>99%). This reaction has the advantages of high efficiency, mild conditions, and environmental friendliness. The obtained chiral N-tert-butylsulfonamide can be deprotected with a sulfonyl protecting group to obtain the corresponding chiral primary amine.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis, specifically to a synthetic method for preparing chiral N-tert-butylsulfonamide compounds by manganese-catalyzed asymmetric hydrogenation of N-tert-butylsulfonamide compounds. Background Technology

[0002] Chiral amines are a very important class of organic synthetic intermediates, playing a crucial role in both scientific research and industrial production. [(a) Kobayashi, S.; Ishitani, H. Chem. Rev. 1999, 99, 1069-1094. (b) McAllister, SD; Rizvi, G.; Anavi-Goffer, S.; Hurst, DP; Barnett-Norris, J.; Lynch, DL; Reggio, PH; Abood, MEJ Med. Chem. 2003, 46, 5] 139-5152.(c)Dorta, R.;Broggini, D.;Stoop, R.;Rüegger, H.;Spindler, F.;Togni, A. Chem. Eur. J. 2004, 10, 267-278.(d)Wang, A.;Prouty, CP;Pelton, PD;Yong, M.;Demarest, KT;Murray, WV;Kuo, G.-H. Bioorg. Med. Chem. Lett. 2010, 20, 1432-1435.]. Transition metal-catalyzed asymmetric hydrogenation of imines is one of the most direct and efficient routes for the preparation of chiral amines. Over the past few decades, noble metal catalytic systems based on Rh, Ru, Ir, and Pd have been widely used in the asymmetric hydrogenation of imines [(e) Tang, W.; Zhang, X. Chem. Rev. 2003, 103, 3029-3070. (f) Zhang, W.; Chi, Y.; Zhang, X. Acc. Chem. Res. 2007, 40, 1278-1290. (g) Johnson, NB; Lennon, I C; Moran, PH; Ramsden, J.Acc. Chem. Res. 2007, 40, 1291-1299.(h) Xie, J.-H.; Zhu, S.-F.; Zhou, Q.-L. Chem. Rev. 2011, 111, 1713-1760.(i) Zhang, Z.; Butt, NA; Zhang, W. Chem. Rev. 2016, 116, 14769-14827.]. However, the extremely low abundance of these precious metals on Earth, their high cost, and their high biotoxicity largely limit their application value. In contrast, abundant transition metal catalysts have the advantages of being inexpensive, low-toxicity, and environmentally friendly in asymmetric catalysis. Therefore, the development of asymmetric hydrogenation of imines catalyzed by abundant metals has broad application prospects.

[0003] In 2021, Liu Qiang et al. first achieved manganese-catalyzed asymmetric hydrogenation of imines using chiral PNN ligands [(j)Liu,C.;Wang,M.;Liu,S.;Wang,Y.;Peng,Y.;Lan,Y.;Liu,Q.Angew.Chem.,Int.Ed.2021,60,5108-5113.]. Subsequently, they successively achieved the asymmetric hydrogenation of various imines using a manganese / chiral PNN ligand catalytic system [(k)Liu,C.;Wang,M.;Xu,Y.;Li,Y.;Liu,Q.Angew.Chem.Int.Ed.2022,61,e202202814.(l)Liu,C.;Liu,X.;Liu,Q.Chem 2023,9,2585-2600.(m)Wang,M.;Liu,S.;Liu,H.;Wang,Y.;Lan,Y.;Liu,Q.Nature 2024,631,556-562.]. Furthermore, Clarke et al. also achieved the asymmetric hydrogenation of in-situ formed imines using manganese / chiral PNN ligands [(n)Oates, CL; Goodfellow, AS; Buhl, M.; Clarke, ML. Green Chem. 2023, 25, 3864-3868.]. However, these reports are limited to electron-rich imines, and highly stereoselective asymmetric hydrogenation of electron-deficient N-sulfonyl imines has not been achieved. Based on this, we developed a method using Mn(CO)5Br and chiral PNN ligands as catalysts to obtain chiral amine compounds with high yields (up to 99%) and high ee values ​​(up to >99%) through the asymmetric hydrogenation of N-tert-butylsulfonyl imines. Summary of the Invention

[0004] The purpose of this invention is to provide a method for synthesizing chiral N-tert-butylsulfonamide compounds. This method provides a highly efficient hydrogenation catalytic system with advantages such as simple operation and high catalytic activity, and has high industrial application value.

[0005] Specifically, this invention provides a method for synthesizing chiral N-tert-butylsulfonamide compounds. This method uses N-tert-butylsulfonylimide and hydrogen as raw materials, employs Mn(CO)₅Br and a chiral PNN ligand as catalysts, and carries out a hydrogenation reaction under conditions of an alcohol solvent and a base additive. This method achieves high yield and high enantioselectivity in the preparation of chiral N-tert-butylsulfonamides. The specific steps are as follows:

[0006] In a glove box, Mn(CO)5Br and chiral PNN ligand were stirred in solution for 1 hour. Then, a solution of an alkaline additive and N-tert-butylsulfonylimide was added, and the mixture was placed in a high-pressure reactor. The reactor was purged with hydrogen three times, and the pressure was increased to 3-5 MPa. The reaction was carried out at 20-80°C for 12-48 hours. After cooling to room temperature, hydrogen was slowly released, the solvent was removed, and the residue was separated by column chromatography to obtain chiral N-tert-butylsulfonamide.

[0007]

[0008] R, R 1 Selected independently from hydrogen, C1-C 40 (preferably C1-C) 30 More preferably, it has a C1-C6 alkane group and a ring carbon number of C3-C6. 12 (Preferably C3-C8, more preferably C3-C6) one or more of cycloalkyl, phenyl and substituted phenyl, benzyl and substituted benzyl; wherein the phenyl and the substituents of the benzyl are each independently selected from C1-C6. 40 (preferably C1-C) 30 More preferably, it is a C1-C6 alkane group, C1-C 40 (preferably C1-C) 30 More preferably, C1-C6) alkoxy, halogen, C1-C 40 (preferably C3-C) 30 More preferably C3-C 24 One or more of the following: ester group, cyano group; R, R 1 They can be the same or different groups. R on the benzene ring 1 The number is 1-6 (preferably 1-5, more preferably 1-3).

[0009] The chiral PNN ligand (L*) PNN Its general structural formula is as follows: R c The absolute configuration representing central chirality is type R, S p The absolute configuration representing planar chirality is the S-type.

[0010]

[0011] In the formula:

[0012] R represents hydrogen and C1-C, respectively. 40 (preferably C1-C) 30 More preferably, it is a C1-C6 alkane group with C6-C6 carbons on the aromatic ring. 60 (preferably C6-C) 30 More preferably C6-C 24The aromatic group (the aromatic group is phenyl, 2-substituted, 3-substituted, 4-substituted, 2,6-disubstituted or 2,4,6-trisubstituted aryl, wherein the substituent is C1-C) 40 (preferably C1-C) 30 More preferably, it is a C1-C6 alkane group, C1-C 40 (preferably C1-C) 30 More preferably, it is one or more of (C1-C6) alkoxy, halogen, nitro, ester or cyano groups, or an aromatic ring containing one or more N, S, O, or P heteroatoms with a carbon number of C3-C6. 60 Aromatic group (the aromatic group is phenyl, 2-substituted, 3-substituted, 4-substituted, 2,6-disubstituted, or 2,4,6-trisubstituted aryl, wherein the substituent is C1-C2). 40 (preferably C1-C) 30 More preferably, it is a C1-C6 alkane group, C1-C 40 (preferably C1-C) 30 More preferably, it is a C1-C6) alkoxy group, halogen, nitro group, or C1-C6 group. 40 (preferably C3-C) 30 More preferably C3-C 24 One or more of the following: ester group or cyano group;

[0013] The chiral PNN ligand (L*) PNN The preferred option is L* PNN -3.

[0014]

[0015] The reaction medium is at least one or more of toluene, benzene, methanol, ethanol, isopropanol, dichloromethane, dichloroethane, carbon tetrachloride, ethyl acetate, diethyl ether, tetrahydrofuran, dimethyl sulfoxide, or N,N-dimethylformamide. Ethanol is preferred.

[0016] The alkaline additive is selected from... i Pr2NEt、 i PrNMe2, NEt3, DMAP, KOH, NaOH, Na2CO3, Cs2CO3, K2CO3, NaHCO3, t BuOK t BuONa t One or more of BuOLi, MeONa, or K3PO4; preferably Na2CO3.

[0017] The molar ratio of N-tert-butylsulfonylimide to the alkali additive is 10-1000:1 (preferably 10-500:1, more preferably 10-100:1).

[0018] The molar ratio of N-tert-butylsulfonylimide to Mn(CO)5Br is 100-50000:1 (preferably 100-5000:1, more preferably 100-1000:1).

[0019] The N-tert-butylsulfonylimide and chiral PNN ligand (L*) PNN The molar ratio of ) is 100-50000:1 (preferably 100-5000:1, more preferably 100-1000:1).

[0020] The reaction temperature is 20-80℃ (preferably 20-60℃, more preferably 20-40℃).

[0021] The reaction time is 12-48h (preferably 12-36h, more preferably 12-24h).

[0022] In this invention, a hydrogenation reaction is carried out under this homogeneous catalytic system to obtain chiral N-tert-butylsulfonamide compounds in high yield (>99%) and high ee value (>99%).

[0023] This reaction has the advantages of high efficiency, mild conditions, and environmental friendliness. The resulting chiral N-tert-butylsulfonamide can be deprotected with a sulfonyl protecting group to yield the corresponding chiral primary amine. Attached Figure Description

[0024] The accompanying drawings, which form part of this specification, are used to provide a further understanding of the invention. The illustrative embodiments of the invention and their descriptions are used to explain the invention and do not constitute an undue limitation of the invention. Hereinafter, embodiments of the invention will be described in detail with reference to the accompanying drawings, wherein:

[0025] Figure 1 The 1H NMR spectrum of (S)-2-methyl-N-(1-phenylethyl)propane-2-sulfonamide II-a prepared in Example 1;

[0026] Figure 2 The carbon NMR spectrum of (S)-2-methyl-N-(1-phenylethyl)propane-2-sulfonamide II-a prepared in Example 1. Detailed Implementation

[0027] The present invention will be further illustrated below with reference to specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Experimental methods in the following embodiments, unless otherwise specified, are generally performed under conventional conditions or as recommended by the manufacturer.

[0028] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of skill in the art. The reagents and raw materials used in this invention are readily available through conventional means, and unless otherwise specified, they are used in accordance with conventional methods or product instructions. Furthermore, any methods and materials similar to or equivalent to those described herein may be applied to the methods of this invention. The preferred embodiments and materials described herein are for illustrative purposes only. The nuclear magnetic resonance (NMR) measurements in this embodiment of the invention were performed using a Bruker 400M NMR spectrometer.

[0029] The preparation method of N-tert-butylsulfonylimide I is referenced in [(o)Li,B.; Chen,J.; Zhang,Z.; Gridnev,ID; Zhang,W. Angew. Chem. Int. Ed. 2019,58,7329-7334.]. Chiral PNN ligands (L* PNN The preparation method is described in reference [(p)Wan, Y.-B.;Hu, X.-P.ACS Catal.2024,14,17633-17641.]. Chiral N-tert-butylsulfonamide II is a known product, as detailed in reference [(o)Li, B.;Chen, J.;Zhang, Z.;Gridnev, ID;Zhang, W.Angew.Chem.Int.Ed.2019,58,7329-7334.].

[0030] I. Example

[0031] Example 1

[0032] Chiral (S)-2-methyl-N-(1-phenylethyl)propane-2-sulfonamide II-a was prepared from (E)-2-methyl-N-(1-phenylethyl)propane-2-sulfonamide Ia.

[0033]

[0034] In a glove box, Mn(CO)₅Br (0.0015 mmol, 0.4 mg) was reacted with chiral PNN (L*). PNN -3) A 1 mL ethanol solution of the ligand (0.00165 mmol, 1.0 mg) was stirred for 1 hour. Then, a 1 mL ethanol solution of Na₂CO₃ (0.015 mmol, 1.6 mg) and (E)-2-methyl-N-(1-phenylethylidene)propane-2-sulfonamide Ia (0.15 mmol, 35.9 mg) was added, wherein Mn(CO)₅Br: chiral PNN(L*) PNN-3) The molar ratio of ligand Na₂CO₃ to Ia was 1:1.1:10:100. The mixture was placed in a high-pressure reactor, purged three times with hydrogen, and purged to 5 MPa. The reaction was carried out at 40°C for 12 hours. After cooling to room temperature, the hydrogen was slowly released, the solvent was removed, and the residue was separated by column chromatography. The reaction yielded (S)-2-methyl-N-(1-phenylethyl)propane-2-sulfonamide II-a in 99% yield and 95% ee.

[0035] The 1H and 1C NMR spectra of (S)-2-methyl-N-(1-phenylethyl)propane-2-sulfonamide II-a are as follows: Figure 1 , 2 As shown: 1 H NMR (400MHz, CDCl3) δ7.29-7.23(m,4H),7.21-7.17(m,1H),4.66-4.55(m,2H),1.50(d,J=8.0Hz,3H),1.23(s,9H); 13 C NMR (101MHz, CDCl3) δ143.6,128.8,127.4,125.9,59.8,54.5,25.7,24.2.[α] D 20 = -21.8 (c 0.32, CH2Cl2).

[0036] Example 2

[0037] The ethanol in Example 1 was replaced by an equal volume of tetrahydrofuran, with the remaining procedures and conditions the same as in Example 1. The reaction yielded (S)-2-methyl-N-(1-phenylethyl)propane-2-sulfonamide II-a in 99% yield and 75% ee.

[0038] Example 3

[0039] The chiral PNN(L*) in Example 1 PNN -3) Ligands are chiral PNN(L*) PNN -1) The ligand was replaced in equimolar amounts, and the rest of the process and conditions were the same as in Example 1. The reaction yielded (S)-2-methyl-N-(1-phenylethyl)propane-2-sulfonamide II-a in 99% yield and 41% ee.

[0040]

[0041] Example 4

[0042] The chiral PNN(L*) in Example 1 PNN -3) Ligands are chiral PNN(L*) PNN-2) The tridentate ligand was replaced in equimolar amounts, and the remaining process and conditions were the same as in Example 1. The reaction yielded (S)-2-methyl-N-(1-phenylethyl)propane-2-sulfonamide II-a in 98% yield and 45% ee.

[0043]

[0044] Example 5

[0045] The chiral PNN(L*) in Example 1 PNN -3) Ligands are chiral PNN(L*) PNN -4) The ligand was replaced in equimolar amounts, and the rest of the process and conditions were the same as in Example 1. The reaction yielded (S)-2-methyl-N-(1-phenylethyl)propane-2-sulfonamide II-a in 99% yield and 82% ee.

[0046]

[0047] Example 6

[0048] The chiral PNN(L*) in Example 1 PNN -3) Ligands are chiral PNN(L*) PNN -5) The ligand was replaced in equimolar amounts, and the rest of the process and conditions were the same as in Example 1. The reaction yielded (S)-2-methyl-N-(1-phenylethyl)propane-2-sulfonamide II-a in 99% yield and 82% ee.

[0049]

[0050] Example 7

[0051] The reaction time of 12 h in Example 1 was replaced with 24 h, and the rest of the process and conditions were the same as in Example 1. The reaction yielded (S)-2-methyl-N-(1-phenylethyl)propane-2-sulfonamide II-a in 99% yield and 95% ee.

[0052] Example 8

[0053] The reaction temperature of 40°C in Example 1 was replaced with 20°C, and the rest of the process and conditions were the same as in Example 1. The reaction yielded (S)-2-methyl-N-(1-phenylethyl)propane-2-sulfonamide II-a in 97% yield and 95% ee.

[0054] Example 9

[0055] The alkaline additive Na2CO3 from Example 1 was used... t BuOK was substituted in equal molar amounts, and the remaining process and conditions were the same as in Example 1. The reaction yielded (S)-2-methyl-N-(1-phenylethyl)propane-2-sulfonamide II-a in 99% yield and 94% ee.

[0056] Example 10

[0057] The alkali additive Na₂CO₃ (0.015 mmol, 1.6 mg) in Example 1 was replaced with Na₂CO₃ (0.0075 mmol, 0.8 mg), and the remaining procedures and conditions were the same as in Example 1. The reaction yielded (S)-2-methyl-N-(1-phenylethyl)propane-2-sulfonamide II-a in 97% yield and 95% ee.

[0058] Example 11

[0059] The Mn(CO)5Br (0.0015 mmol, 0.4 mg) in Example 1 was replaced with Mn(CO)5Br (0.00075 mmol, 0.2 mg), and the remaining procedures and conditions were the same as in Example 1. The reaction yielded (S)-2-methyl-N-(1-phenylethyl)propane-2-sulfonamide II-a in 99% yield and 95% ee.

[0060] Example 12

[0061] The chiral PNN(L*) in Example 1 PNN -3) Tridentate ligand (0.00165 mmol, 1.0 mg) with PNN (L* PNN -3) The tridentate ligand (0.000825 mmol, 0.5 mg) was substituted, and the rest of the process and conditions were the same as in Example 1. The reaction yielded (S)-2-methyl-N-(1-phenylethyl)propane-2-sulfonamide II-a in 99% yield and 95% ee.

[0062] Example 13

[0063] The Ia in Example 1 was replaced with an equimolar amount of Ib, and the rest of the process and conditions were the same as in Example 1. The reaction yielded (S)-2-methyl-N-(1-(o-tolyl)ethyl)propane-2-sulfonamide II-b in 99% yield and 99% ee. 1 H NMR (400MHz, CDCl3) δ7.33 (d, J = 8.0Hz, 1H), 7.28-7.21 (m, 1H), 7.20-7.12 (m, 2H), 4.95 -4.86(m,1H),4.68(d,J=16.0Hz,1H),2.36(s,3H),1.50(d,J=8.0Hz,3H),1.25(s,9H); 13 C NMR (101MHz, CDCl3) δ142.6,134.2,130.8,127.6,126.9,125.1,59.8,50.5,25.6,24.3,19.2.[α] D20 = -22.5 (c 0.35, CH2Cl2).

[0064]

[0065] Example 14

[0066] The Ia in Example 1 was replaced with an equimolar amount of Ic, and the rest of the process and conditions were the same as in Example 1. The reaction yielded (S)-N-(1-(4-methoxyphenyl)ethyl)-2-methylpropane-2-sulfonamide II-c in 98% yield and 93% ee. 1 H NMR(400MHz, CDCl3) δ7.25(d,J=8.0Hz,2H),6.86(d,J=8.0Hz,2H),4.69-4.58( m,1H),4.40(d,J=8.0Hz,1H),3.81(s,3H),1.56(d,J=8.0Hz,3H),1.31(s,9H); 13 C NMR (101MHz, CDCl3) δ159.2,136.1,127.3,114.2,60.1,55.6,54.4,25.8,24.4.[α] D 20 = -26.8 (c 0.32, CH2Cl2).

[0067]

[0068] Example 15

[0069] The Ia in Example 1 was replaced with an equimolar amount of Id, and the rest of the process and conditions were the same as in Example 1. The reaction yielded (S)-2-methyl-N-(1-(naphthyl-2-yl)ethyl)propane-2-sulfonamide II-d in 97% yield and >99% ee. 1 H NMR (400MHz, CDCl3) δ7.85 (t, J = 8.0Hz, 3H), 7.73 (s, 1H), 7.53-7.40 (m, 3H), 4.88-4.81(m,1H),4.39(d,J=8.0Hz,1H),1.66(d,J=8.0Hz,3H),1.33(s,9H); 13 C NMR (101MHz, CDCl3) δ141.2,133.6,133.1,129.2,128.2,127.9,126.7,126.3,124.8,124.5,60.1,54.9,25.8,24.5.[α] D 20 = -55.6 (c 0.28, CH2Cl2).

[0070]

[0071] Example 16

[0072] The Ia in Example 1 was replaced with an equimolar amount of Ie, and the rest of the process and conditions were the same as in Example 1. The reaction yielded (S)-2-methyl-N-(1-phenylpropyl)propane-2-sulfonamide II-e in 98% yield and 95% ee. 1 H NMR(400MHz, CDCl3)δ7.34(t,J=8.0Hz,2H),7.29-7.20(m,3H),4.68(d,J=8.0Hz ,1H),4.43–4.33(m,1H),1.86-1.82(m,2H),1.26(s,9H),0.90(t,J=8.0Hz,3H); 13 C NMR (101MHz, CDCl3) δ142.7,128.9,127.5,126.7,60.5,59.9,32.7,24.5,11.0.[α] D 20 = -33.6 (c 0.42, CH2Cl2).

[0073]

[0074] Example 17

[0075] The chiral Mn(CO)5Br in Example 1 was replaced by an equimolar amount of chiral [Ir(COD)Cl]2, with the remaining procedures and conditions the same as in Example 1. The reaction yielded (S)-2-methyl-N-(1-phenylethyl)propane-2-sulfonamide II-a in 98% yield and 12% ee.

[0076] II. Application Examples

[0077] Application Example 1

[0078] (S)-II-a (1.0 mmol, 1.0 equiv., 241.1 mg) and anisole (1.3 mmol, 1.3 equiv., 104.5 mg) were dissolved in 8 mL of dry dichloromethane. Then, aluminum trichloride (2.6 mmol, 2.0 equiv., 346.6 mg) was added in a single addition. After reacting at room temperature for 2 hours, the mixture was diluted with 20 mL of dichloromethane, and then slowly added with 50 mL of aqueous sodium hydroxide solution (2 M). The organic phase was separated, and the aqueous phase was extracted six times with dichloromethane. The combined organic phases were dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was separated by column chromatography. The reaction yielded (S)-phenylethylamine III-a in 95% yield and with 95% ee. (S)-Phenylacetamine III-a is a known product; see references [(q)Gallardo-Donaire, J.; Hermsen, M.; Wysocki, J.; Ernst, M.; Rominger, F.; Trapp, O.; Hashmi, ASK; A.; Comba, P.; Schaub, TJAm.Chem.Soc.2018,140,355-361.].

[0079]

[0080] (S)-Phenylacetamine III-a is an important intermediate for pharmaceutically active IDH1 inhibitors, as detailed in the reference [(r)Levell, JR; Caferro, T.; Chenail, G.; Dix, I.; Dooley, J.; Firestone, B.; Fortin, PD; Giraldes, J.; Gould, T.; Growney, JD; Jones, MD; Kulatila, R.; Lin, F.; Liu, G.; Mueller, A.; van der Plas, S.; Slocum, K.; Smith, T.; Terranova, R.; Touré, BB; Tyagi, V.; Wagner, T.; Xie, X.; Xu, M.; Yang, FS; Zhou, LX; Pagliarini, R.; Cho, YSACSMed.Chem.Lett.2017, 2, 151-156.].

[0081]

[0082] The above-described embodiments are merely examples illustrating implementation methods of the present invention and are not intended to limit the present invention. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art can still modify the technical solutions described in the foregoing embodiments or make equivalent substitutions for some of the technical features. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A method for preparing chiral N-tert-butylsulfonamide compounds by manganese-catalyzed asymmetric hydrogenation, characterized in that: Using N-tert-butylsulfonylimide and hydrogen as raw materials, in the reaction of Mn(CO)5Br with chiral PNN ligand (L*) PNN Under the catalytic system of ), hydrogenation is carried out to obtain chiral N-tert-butylsulfonamide compounds.

2. The method according to claim 1, characterized in that: The racemic chiral diaryl nitroketone compound has the following structure: R, R 1 Selected independently from hydrogen, C1-C 40 (preferably C1-C) 30 More preferably, it has a C1-C6 alkane group and a ring carbon number of C3-C6. 12 (Preferably C3-C8, more preferably C3-C6) one or more of cycloalkyl, phenyl and substituted phenyl, benzyl and substituted benzyl; the substituents on the substituted phenyl and substituted benzyl are each independently selected from C1-C6. 40 (preferably C1-C) 30 More preferably, it is a C1-C6 alkane group, C1-C 40 (preferably C1-C) 30 More preferably, it is a C1-C6 alkoxy group, a halogen (one or more of F, Cl, Br, I), a nitro group, or a C1-C6 group. 40 (preferably C3-C) 30 More preferably C3-C 24 One or more of the following: ester group or cyano group; R, R 1 They are the same or different groups; R on the benzene ring 1 The number is 1-6 (preferably 1-5, more preferably 1-3).

3. The method according to claim 1, characterized in that: The chiral N-tert-butylsulfonamide has the following structure: R, R 1 Selected independently from hydrogen, C1-C 40 (preferably C1-C) 30 More preferably, it has a C1-C6 alkane group and a ring carbon number of C3-C6. 12 (Preferably C3-C8, more preferably C3-C6) one or more of cycloalkyl, phenyl and substituted phenyl, benzyl and substituted benzyl; the substituents on the substituted phenyl and substituted benzyl are each independently selected from C1-C6. 40 (preferably C1-C) 30 More preferably, it is a C1-C6 alkane group, C1-C 40 (preferably C1-C) 30 More preferably, it is a C1-C6 alkoxy group, a halogen (one or more of F, Cl, Br, I), a nitro group, or an ester group (C2-C6). 40 (preferably C3-C) 30 More preferably C3-C 24 or one or more of the following: ) or cyano; R, R 1 They are the same or different groups; R on the benzene ring 1 The number is 1-6 (preferably 1-5, more preferably 1-3).

4. The method according to claim 1, characterized in that: The chiral PNN(L*) PNN The general structural formula of the ligand is as follows: S c or R c The absolute configuration indicating central chirality is either S or R type, where S... p or R p The absolute configuration representing planar chirality is either S or R type; In the formula: R represents hydrogen and C1-C, respectively. 40 (preferably C1-C) 30 More preferably, it is a C1-C6 alkane group with C6-C6 carbons on the aromatic ring. 60 (preferably C6-C) 30 More preferably C6-C 24 The aromatic group, or the aromatic ring containing one or more N, S, O, or P heteroatoms, with a carbon number of C3-C4. 60 One or more of the aromatic groups; The aromatic group is phenyl, or one or more of aryl groups selected from 2-substituted, 3-substituted, 4-substituted, 2,6-disubstituted, or 2,4,6-trisubstituted, and the substituent is C1-C2. 40 (preferably C1-C) 30 More preferably, it is a C1-C6 alkane group, C1-C 40 (preferably C1-C) 30 More preferably, it is a C1-C6 alkoxy group, a halogen (one or more of F, Cl, Br, I), a nitro group, or a C2-C6 group. 40 (preferably C3-C) 30 More preferably C3-C 24 One or more of the ester or cyano groups.

5. The method according to claim 1 or 4, characterized in that: The chiral PNN ligand (L*) PNN The preferred option is L* PNN -3.

6. The method according to claim 1, characterized in that: The reaction medium is at least one or more of toluene, benzene, methanol, ethanol, isopropanol, dichloromethane, dichloroethane, carbon tetrachloride, ethyl acetate, diethyl ether, tetrahydrofuran, dimethyl sulfoxide, or N,N-dimethylformamide; preferably ethanol. The alkaline additive is selected from... i Pr2NEt、 i PrNMe2, NEt3, DMAP, KOH, NaOH, Na2CO3, Cs2CO3, K2CO3, NaHCO3, t BuOK t BuONa t One or more of BuOLi, MeONa, or K3PO4; preferably Na2CO3.

7. The method according to claim 1, characterized in that: The molar ratio of N-tert-butylsulfonylimide to the alkali additive is 10-1000:1 (preferably 10-500:1, more preferably 10-100:1); The molar ratio of N-tert-butylsulfonylimide to Mn(CO)5Br is 100-50000:1 (preferably 100-5000:1, more preferably 100-1000:1); The N-tert-butylsulfonylimide and chiral PNN ligand (L*) PNN The molar ratio of ) is 100-50000:1 (preferably 100-5000:1, more preferably 100-1000:1).

8. The synthesis method according to claim 1, characterized in that: The reaction temperature is 20-80℃ (preferably 20-60℃, more preferably 20-40℃).

9. The synthesis method according to claim 1 or 8, characterized in that: The reaction time is 12-48h (preferably 12-36h, more preferably 12-24h).

10. The synthesis method according to claim 1, characterized in that: The specific process of this method is as follows: In a glove box, Mn(CO)5Br is reacted with the chiral PNN ligand (L*). PNN The solution was stirred for 0.5-2 hours, then the alkali additive and the solution of N-tert-butylsulfonamide were added, and the mixture was placed in a high-pressure reactor. The atmosphere inside the reactor was replaced with hydrogen, and the hydrogen was purged to 3-5 MPa. The reaction was carried out at 20-80°C for 12-48 hours. The reactor was cooled to room temperature to release the hydrogen, and the solvent was removed. The residue was separated by column chromatography to obtain chiral N-tert-butylsulfonamide.

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