Co-Cu combined catalysis non-activated mixed olefin corresponding selectivity far-end boron amination reaction method

Abstract

The invention relates to the technical field of organic compound synthesis, in particular to a Co-Cu combined catalysis non-activated mixed olefin enantioselective far-end boron amination reaction method, and develops a stable and reliable Co-Cu bimetallic relay catalysis strategy. According to the strategy, boron and nitrogen-containing functional groups can be enantioselectively embedded into typical remote low activation sites of molecules, a series of unactivated terminal olefin, internal olefin and unrefined olefin isomer mixtures can be effectively converted into value-added chiral organic amination products, and the yield is medium to excellent; the diastereoselectivity and the enantiomer control level are generally very good.

Description

Technical Field

[0001] The invention relates to the technical field of organic compound synthesis, and in particular to a Co-Cu combined catalytic non-activated mixed olefin enantioselective remote boroamination reaction method. Background Art

[0002] In 2013, Hirano, Miura et al. first reported the boroamination of styrene under mild conditions by selectively adding B and N groups to CC unsaturated molecules. However, only moderate to high enantioselectivity (yield 72%, ee 86%) was observed in limited examples. For details, please refer to J.Am.Chem.Soc.2013,135,4934-4937. In 2019, Zhang's group used their own chiral ligands to obtain piv ZPhos achieved the Cu-catalyzed enantioselective boroamination of E-type styrene (yield 70%, ee>98%). The reaction equation is as follows: Figure 1 shown.

[0003] However, the above reaction has high requirements for olefin substrates, and most of them are trans-olefins, which are not easy to obtain from the perspective of synthesis and separation. Moreover, its chiral ligand is not a commercial ligand, and it is difficult to use a preparative-grade liquid phase to separate enantiomers. From the perspective of product purification and separation, these methods are difficult to separate and purify, and most of the products obtained are derivatives of B oxidized to -OH, which undoubtedly limits its further application and derivatization in the later stage. Summary of the invention

[0004] In view of the above-mentioned deficiencies in the prior art, the purpose of the present invention is to provide a Co-Cu co-catalyzed enantioselective distal boroamination method for non-activated mixed olefins. The present invention uses bimetallic relay catalysis to realize the distal bond asymmetric boroamination of non-activated olefins for the first time. The reaction is promoted by in-situ generated Co-H and then a Cu-catalyzed asymmetric boroamination reaction. This method can introduce two functional groups into the substrate at one time, and effectively construct carbon bonds and carbon-nitrogen bonds with excellent enantio- and diastereoselectivity.

[0005] In order to solve the above technical problems, the present invention adopts the following technical solutions:

[0006] A Co-Cu co-catalyzed enantioselective remote boroamination reaction method for non-activated olefins comprises the following steps:

[0007] Under a protective atmosphere, lithium tert-butoxide LiO t Bu is the substrate, CuCl is the catalyst, (S,S)- iPr-phosferrox is a chiral ligand, and the mixed reaction is activated to obtain a copper catalytic system.

[0008] In tetrahydrofuran solvent, LiO t Bu, B2pin2 and 4-phenyl-1-butene derivatives are substrates, B2pin2 is a reducing agent, CoBr2 is a catalyst, (S,S)-Ph-BPE is a chiral ligand, and the mixed reaction is activated to obtain a cobalt catalytic system.

[0009] The copper catalytic system is added to the cobalt catalytic system, and a derivative of N,N-dialkylhydroxylamine is added to the mixed reaction system to introduce nitrogen functional groups. CoBr2 is reacted with LiO t Under the action of Bu and B2pin2, divalent Co is reduced to generate the first intermediate Co-Bpin, which undergoes migration insertion and β-H elimination with a mixed olefin of a 4-phenyl-1-butene derivative to obtain a second intermediate Co-H, which undergoes continuous migration insertion and β-H elimination with a 4-phenyl-1-butene derivative to obtain a trans olefin of a single configuration, completing the Co catalytic cycle; then the trans olefin of a single configuration enters the Cu catalytic system for cyclic catalysis, and the trans olefin of a single configuration undergoes selective migration insertion with the Cu-Bpin intermediate in the copper catalytic system to obtain a fourth intermediate, and then the fourth intermediate undergoes oxidative addition reduction elimination with a derivative of N,N-dialkylhydroxylamine to obtain the target product, thereby realizing the enantioselective remote boroamination reaction of non-activated olefins.

[0010] The reaction synthesis route is as follows:

[0011]

[0012] Among them, the structural formula of (S,S)-Ph-BPE is (S,S)- i The structural formula of Pr-phosferrox is

[0013] 3a can be selected from the following compounds:

[0014]

[0015] In a preferred embodiment of the present invention, in the copper catalyst system, CuCl, (S,S)-CH2 i Pr-phosferrox, and LiO t The molar ratio of Bu is 1:1.2:36.

[0016] In a preferred embodiment of the present invention, LiO tThe usage ratio of Bu to tetrahydrofuran is 0.36mmol:0.5mL.

[0017] In a preferred embodiment of the present invention, in the cobalt catalyst system, the molar ratio of CoBr2, (S,S)-Ph-BPE, B2pin2 and 4-phenyl-1-butene derivative is 1:1.2:40:20.

[0018] In a preferred embodiment of the present invention, LiO t The usage ratio of Bu, 4-phenyl-1-butene derivative and tetrahydrofuran is 0.04 mol:0.2 mmol:0.5 mL.

[0019] In a preferred embodiment of the present invention, the molar ratio of the derivative of N,N-dialkylhydroxylamine to CuCl is 0.3:0.01, and the molar ratio of the derivative of N,N-dialkylhydroxylamine to CoBr2 is 0.3:0.01.

[0020] In a preferred embodiment of the present invention, the volume ratio of the copper catalyst system to the cobalt catalyst system is 1:1.

[0021] In a preferred embodiment of the present invention, the activation time of the copper catalyst system and the cobalt catalyst system is 30 minutes, and the reaction temperature is 23°C to 28°C.

[0022] In a preferred embodiment of the present invention, after the reaction is completed, the reaction is quenched with water, extracted, concentrated in vacuo, and the residue is purified by neutral Al2O3 or amino silica gel column chromatography.

[0023] Compared with the prior art, the present invention has the following beneficial effects:

[0024] 1. The present invention uses bimetallic relay catalysis to realize the remote asymmetric boroamination reaction of unactivated olefins for the first time. The reaction is promoted by in situ generated Co-H and then by a reversible continuous β-H elimination / olefin insertion, followed by a Cu-catalyzed asymmetric boroamination reaction. This method can introduce two functional groups into the substrate at one time, effectively constructing carbon-boron bonds and carbon-nitrogen bonds with excellent enantio- and diastereo-selectivity. The reaction principle diagram is shown in the figure below. Figure 2 As shown, the reaction principle is:

[0025] In tetrahydrofuran solvent, CoBr2 in LiO tUnder the action of Bu and B2pin2, the divalent Co catalyst L*Co(II) is reduced to form an L*Co(I)-Bpin intermediate, which undergoes migration insertion and β-H elimination with a mixed olefin substrate to obtain intermediate I. Subsequently, intermediate I undergoes continuous migration insertion and β-H with a mixed olefin substrate to obtain a thermodynamically stable intermediate 1' and regenerate intermediate I, completing the first Co catalytic cycle; intermediate 1'III then enters the next Cu catalytic cycle, undergoes selective migration insertion with the L*Cu-Bpin species generated in the system to obtain intermediate V, and then intermediate V undergoes oxidative addition reduction elimination with a derivative of N,N-dialkylhydroxylamine to obtain the target product and alkoxycopper intermediate VI, and then intermediate VI undergoes σ double decomposition with B2pin2 to obtain L*Cu-Bpin species, completing the second Cu catalytic cycle.

[0026] 2. Compared with the existing methods, ① the Co-Cu synergistic catalytic scheme of the present invention uses various unactivated terminal olefins, internal olefins and a mixture of olefin isomers with low reactivity at the distal end to carry out enantioselective boroamination reactions, and has a wide range of applications; ② the present invention uses commercially available chiral ligands and commercially available neutral Al2O3 or reusable amino silica gel as column chromatography fillers to separate the products, and can successfully obtain the target compound rather than the oxidized derivative, which provides a broader space for its subsequent application and derivatization; ③ the method of the present invention can successfully install the boron-containing functional group and the nitrogen-containing functional group at the less active C(sp3)-H site far from the initial C=C bond with enantioselectivity. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1 It is the reaction equation of the prior art.

[0028] Figure 2 The figure is a schematic diagram of the reaction principle of the present invention. DETAILED DESCRIPTION

[0029] The following is a detailed description of the technical solutions in the embodiments of the present invention in combination with preferred embodiments and data. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0030] It should be noted that all professional terms used in the present invention are only for the purpose of describing specific embodiments and are not intended to limit the scope of protection of the present invention. Unless otherwise specifically stated, various raw materials, reagents, instruments and equipment used in the following embodiments of the present invention can be purchased from the market or prepared by existing methods.

[0031] In the reaction system of the present invention, other soluble copper salts and soluble cobalt salts are also tried as catalysts. They can also react, but the effect is not as good as the combination of CuCl and CoBr2. The specific screening process is as follows:

[0032]

[0033] The cobalt salt screening process is shown in Table 1:

[0034] Table 1 Cobalt salt screening process

[0035]

[0036]

[0037] The copper salt screening process is shown in Table 2:

[0038] Table 2 Copper salt screening process

[0039]

[0040] Example 1

[0041]

[0042] In a glove box filled with nitrogen, CoBr2 (2.2 mg, 0.01 mmol, 5 mol%), chiral ligand (S,S)-Ph-BPE (6.0 mg, 0.012 mmol, 6.0 mol%), substrate lithium tert-butoxide (LiO t Bu) (3.2 mg, 0.04 mmol, 20.0 mol%), (bis(pinacol)diboron) B2pin2 (101.6 mg, 0.4 mmol, 2 equiv), 4-phenyl-1-butene (0.2 mmol, 1 equiv) and anhydrous tetrahydrofuran (0.5 mL) were added, and the solution was stirred for 30 minutes.

[0043] In another identical reaction flask, add CuCl (1.0 mg, 0.01 mmol, 5.0 mol%), chiral ligand (S, S)-CH2 i Pr-phosferrox (6.0 mg, 0.012 mmol, 6 mol%), anhydrous tetrahydrofuran (0.5 mL), LiOt Bu (28.8 mg, 0.36 mmol, 1.8 equiv) and stirred for 30 minutes.

[0044] Then, the vial of the copper catalyst system was added to the vial of the cobalt catalyst system, and finally, the N,N-dialkylhydroxylamine derivative 3a (0.3 mmol, 1.5 equiv) was added to the mixed reaction system. The reaction system was taken out of the glove box, stirred at 25 °C for 36 h, quenched with water, extracted with DCM (3×5.0 mL), and the combined organic phases were concentrated in vacuo. The residue was purified by amino silica gel column chromatography to obtain the target product.

[0045] (1S,2R)-N,N-dibenzyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(m-toly l)butan-1-amine.

[0046] 1 H NMR(600MHz,Chloroform-d)δ7.41(d,J=J=7.8Hz,4H),7.26(t,J=7.8Hz,5H),7.19(t,J =7.2Hz,2H),7.10(d,J=7.8Hz,1H),6.94(d,J=7.2Hz,1H),6.91(s,1H),3.96(d,J=13.8 Hz,2H),3.89(d,J=12.2Hz,1H),2.94(d,J=13.8Hz,2H),2.37(s,3H),2.00–1.95(m,1H) ,1.39(s,6H),1.38(s,6H),1.15–1.11(m,1H),1.03–0.99(m,1H),0.79(t,J=7.2Hz,3H).

[0047] 13 C NMR(150MHz,Chloroform-d)δ139.98,137.09,136.64,130.50,129.26,127.84,127. 60,127.57,126.52,126.45,83.20,64.78,54.27,25.83,25.50,22.66,21.71,13.58.

[0048] 11 B NMR(193MHz,Chloroform-d)δ33.89.

[0049] HRMS(ESI-TOF)(m / z):Calcd for C31 H 40 BNO2([M+H] + ), 469.3152, found: 469.3149.

[0050] Mp: 65 - 67 °C

[0051] HPLC analysis (OD - H, Hexane / IPA = 95 / 5, 1.0 mL / min, 254 nm) indicated 94% ee: tR (major) = 4.43 min, tR (minor) = 5.13 min.

[0052] [α] D (25.0 °C, c = 1.0 in CH2Cl2) = -90.64.

[0053] Example 2

[0054]

[0055] (1S,2R)-N,N - dibenzyl - 1 - (3 - methoxyphenyl) - 2 - (4,4,5,5 - tetramethyl - 1,3,2 - dioxaborolan - 2 - yl)butan - 1 - amine

[0056] 1 1H NMR (500 MHz, Chloroform - d) δ 7.41 (d, J = 7.5 Hz, 4H), 7.29–7.24 (m, 5H), 7.19 (t, J = 7.0 Hz, 2H), 6.84 (d, J = 8.0 Hz, 1H), 6.74 (d, J = 7.0 Hz, 1H), 6.66 (s, 1H), 3.97 (d, J = 13.5 Hz, 2H), 3.89 (d, J = 12.5 Hz, 1H), 3.80 (s, 3H), 2.97 (d, J = 13.5 Hz, 2H), 1.98–1.92 (m, 1H), 1.39 (s, 6H), 1.38 (s, 6H), 1.18–1.10 (m, 1H), 1.05–1.00 (m, 1H), 0.79 (t, J = 7.5 Hz, 3H).

[0057] 1313C NMR (150 MHz, Chloroform-d) δ 159.23, 139.88, 138.60, 129.23, 128.59, 127.85, 126.56, 121.88, 115.40, 112.12, 83.23, 64.80, 55.12, 54.31, 25.83, 25.49, 22.61, 13.58.5, 129.05, 127.78, 127.56, 126.16,

[0058] 11 11B NMR (193 MHz, Chloroform-d) δ 34.04.

[0059] HRMS (ESI-TOF) (m / z): Calcd for C 31 H 40 BNO3 ([M + H] + ), 485.3101, found: 485.3118.

[0060] Mp: 120 - 123 °C

[0061] HPLC analysis (OD-H, Hexane / IPA = 95 / 5, 1.0 mL / min, 254 nm) indicated 91% ee: tR (major) = 5.90 min, tR (minor) = 8.80 min.

[0062] [α] D (25.0 °C, c = 1.0 in CH2Cl2) = -30.59.

[0063] Example 3

[0064]

[0065] (1S,2R)-N,N-dibenzyl-1-(3-chlorophenyl)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)butan-1-amine

[0066] 11H NMR (500 MHz, Chloroform-d) δ 7.41 (d, J = 7.5 Hz, 4H), 7.31–7.26 (m, 6H), 7.21 (t, J = 7.0 Hz, 2H), 7.11 (s, 1H), 7.01 (d, J = 7.0 Hz, 1H), 3.97 (d, J = 13.5 Hz, 2H), 3.91 (d, J = 12.0 Hz, 1H), 2.92 (d, J = 14.0 Hz, 2H), 1.97–1.91 (m, 1H), 1.40 (s, 6H), 1.38 (s, 6H), 1.16–1.11 (m, 1H), 1.03–0.98 (m, 1H), 0.80 (t, J = 7.0 Hz, 3H).

[0067] 13 13C NMR (150 MHz, Chloroform-d) δ 139.48, 139.18, 133.94, 129.45, 129.23, 129.04, 127.97, 127.48, 127.10, 126.73, 83.33, 64.44, 54.24, 25.84, 25.50, 22.54, 13.52.

[0068] 11 11B NMR (193 MHz, Chloroform-d) δ 36.39.

[0069] HRMS (ESI-TOF) (m / z): Calcd for C 30 H 37 BClNO2 ([M + H] + ), 489.2606, found: 489.2669.

[0070] Mp: 100–112 °C

[0071] HPLC analysis (OD-H, Hexane / IPA = 95 / 5, 1.0 mL / min, 254 nm) indicated 90% ee: tR (major) = 5.43 min, tR (minor) = 7.77 min.

[0072] [α] D (25.0 °C, c = 1.0 in CH2Cl2) = -43.38

[0073] Example 4

[0074]

[0075] (1S,2R)-N,N-dibenzyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(3-(trifl uoromethyl)phenyl)butan-1-amine

[0076] 1 H NMR(500MHz,Chloroform-d)δ7.56(d,J=7.5Hz,1H),7.49(t,J=7.5Hz,1H),7.41(d,J=7.0Hz,4H),7.34(d,J=6.0Hz,2H),7.28(t,J=7.0Hz,4H),7.24–7.20(m,2H),4.00(d,J=13.0Hz,3H),2.85(d,J=13.5Hz,2H),2.02–1.97(m,1H),1.41(s,6H),1.39(s,6H),1.17–1.11(m,1H),1.01–0.94(m,1H),0.80(t,J=7.0Hz,3H).

[0077] 13 C NMR(150MHz,Chloroform-d)δ139.28,137.91,132.17,130.13(q,J=31.8Hz),129.21,128.24,128.00,126.80,126.39(q,J=3.5Hz),124.38(q,J=270.8Hz),123.78(q,J=3.6Hz),83.38,64.39,54.26,25.81,25.49,22.52,13.47.

[0078] 19 F NMR(565MHz,Chloroform-d)δ-62.50.

[0079] 11 B NMR(193MHz,Chloroform-d)δ36.35.

[0080] HRMS(ESI-TOF)(m / z):Calcd for C 31 H 37 BF3NO2([M+H] + ),523.2869,found:523.2818.

[0081] Mp:80-82℃

[0082] HPLC analysis (OD-H, Hexane / IPA = 95 / 5, 1.0 mL / min, 254 nm) indicated 89% ee: tR (major) = 5.00 min, tR (minor) = 7.57 min.

[0083] [α] D (25.0 °C, c = 1.0 in CH2Cl2) = -43.38.

[0084] Example 5

[0085]

[0086] (1S,2R)-N,N-dibenzyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)butan-1-amine

[0087] 1 1H NMR (600 MHz, Chloroform-d) δ 7.74 (d, J = 7.2 Hz, 1H), 7.61 (s, 1H), 7.42 (d, J = 7.2 Hz, 4H), 7.38 (t, J = 7.2 Hz, 1H), 7.26 (t, J = 7.2 Hz, 5H), 7.20 (t, J = 7.2 Hz, 2H), 3.98–3.93 (m, 3H), 2.89 (d, J = 13.8 Hz, 2H), 2.05–2.01 (m, 1H), 1.40 (s, 6H), 1.38 (s, 6H), 1.37 (s, 6H), 1.36 (s, 6H), 1.15–1.12 (m, 1H), 1.04–1.00 (m, 1H), 0.79 (t, J = 7.2 Hz, 3H).

[0088] 13 13C NMR (150 MHz, Chloroform-d) δ 139.91, 136.65, 135.75, 133.17, 131.92, 129.40, 127.81, 127.15, 126.53, 83.68, 83.17, 64.79, 54.31, 25.85, 25.50, 25.09, 24.86, 22.65, 13.59.

[0089] 11 11B NMR (193 MHz, Chloroform-d) δ 35.57, 31.98.

[0090] HRMS(ESI-TOF)(m / z):Calcd for C 36 H 49 B2NO4([M+H] + ),581.3848,found:581.3834.

[0091] HPLC analysis(OD-H,Hexane / IPA=90 / 10,1.0mL / min,254nm)indicated 88%ee:tR(minor)=7.09min,tR(major)=8.97min.

[0092] [α] D (25.0℃,c=1.0 in CH2Cl2)=-16.27.

[0093] Example 6

[0094]

[0095] (3-((1S,2R)-1-(dibenzylamino)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)butyl)phenyl)carbonate

[0096] 1 1H NMR(600MHz,Chloroform-d)δ7.43(d,J=7.5Hz,4H),7.37(t,J=7.5Hz,1H),7.26(t,J=7.5Hz,4H),7.20(t,J=7.5Hz,2H),7.13–7.11(m,1H),7.00(d,J=8.0Hz,1H),6.90(s,1H),3.97(d,J=13.5Hz,2H),3.93(d,J=12.0Hz,1H),2.94(d,J=13.5Hz,2H),1.99–1.93(m,1H),1.59(s,9H),1.41(s,6H),1.39(s,6H),1.18–1.10(m,1H),1.05–0.99(m,1H),0.80(t,J=7.0Hz,3H).

[0097] 1313C NMR (150 MHz, Chloroform-d) δ 151.88, 150.85, 139.67, 138.58, 129.26, 128.53, 127.86, 126.59, 126.46, 122.54, 119.49, 83.40, 83.27, 64.33, 54.17, 27.74, 25.82, 25.50, 22.55, 13.50.

[0098] 11 11B NMR (193 MHz, Chloroform-d) δ 33.99.

[0099] HRMS (ESI-TOF) (m / z): Calcd for C 35 H 46 BNO5 ([M+H] + ), 571.3469, found: 571.3416.

[0100] HPLC analysis (IG, Hexane / IPA = 95 / 5, 1.0 mL / min, 254 nm) indicated 89% ee: tR (major) = 6.93 min, tR (minor) = 14.54 min.

[0101] [α] D (25.0 °C, c = 1.0 in CH2Cl2) = -78.08.

[0102] Example 7

[0103]

[0104] (1S,2R)-1-(benzo[d][1,3]dioxol-5-yl)-N,N-dibenzyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)butan-1-amine

[0105] 11H NMR (600 MHz, Chloroform-d) δ 7.41 (d, J = 7.5 Hz, 4H), 7.26 (t, J = 7.5 Hz, 4H), 7.19 (t, J = 7.0 Hz, 2H), 6.80 (d, J = 8.0 Hz, 1H), 6.68 (s, 1H), 6.54 (d, J = 8.0 Hz, 1H), 5.99 (s, 2H), 3.95 (d, J = 14.0 Hz, 2H), 3.85 (d, J = 12.0 Hz, 1H), 2.97 (d, J = 13.5 Hz, 2H), 1.91–1.86 (m, 1H), 1.40 (s, 6H), 1.38 (s, 6H), 1.18–1.11 (m, 1H), 1.07–1.02 (m, 1H), 0.80 (t, J = 7.5 Hz, 3H).

[0106] 13 13C NMR (150 MHz, Chloroform-d) δ 147.39, 146.30, 139.82, 130.90, 129.19, 127.86, 126.55, 123.22, 109.04, 107.47, 100.84, 83.22, 64.52, 54.24, 25.81, 25.49, 22.60, 13.53.

[0107] 11 11B NMR (193 MHz, Chloroform-d) δ 34.09.

[0108] HRMS (ESI-TOF) (m / z): Calcd for C 31 H 38 BNO4 ([M+H] + ), 499.2894, found: 499.2856.

[0109] Mp: 112 - 114 °C

[0110] HPLC analysis (OD-3, Hexane / IPA = 95 / 5, 1.0 mL / min, 254 nm) indicated 90% ee: tR (major) = 7.57 min, tR (minor) = 8.58 min.

[0111] [α] D (25.0 °C, c = 1.0 in CH2Cl2) = -7.53.

[0112] Example 8

[0113]

[0114] (1S,2R)-1-(benzo[b]thiophen-5-yl)-N,N-dibenzyl-2-(4,4,5,5-tetramethyl-1,3,2-di oxaborolan-2-yl)butan-1-amine

[0115] 1 H NMR(600MHz,Chloroform-d)δ7.64(d,J=2.0Hz,1H),7.50(d,J=8.5Hz,1H),7.43(d,J=7.5Hz,4H),7.34(s,1H),7.27(t,J=7.5Hz,4H),7.20(t,J=7.0Hz,2H),7.08(d,J=8.5Hz,1H),6.80(s,1H),4.05(d,J=12.0Hz,1H),3.99(d,J=14.0Hz,2H),2.96(d,J=14.0Hz,2H),2.06–2.01(m,1H),1.41(s,6H),1.40(s,6H),1.20–1.12(m,1H),1.05–0.97(m,1H),0.80(t,J=7.5Hz,3H).

[0116] 13 C NMR(150MHz,Chloroform-d)δ154.14,145.01,139.93,131.23,127.87,127.02,126.54,125.82,121.81,110.40,106.77,83.23,64.77,54.24,25.84,25.52,22.72,13.55.

[0117] 11 B NMR(193MHz,Chloroform-d)δ33.41.

[0118] HRMS(ESI-TOF)(m / z):Calcd for C 32 H 38 BNO2S([M+H] + ),511.2716,found:511.2758.

[0119] Mp:138-140℃

[0120] HPLC analysis (OD-3, Hexane / IPA = 95 / 5, 1.0 mL / min, 254 nm) indicated 90% ee: tR (major) = 6.11 min, tR (minor) = 6.97 min.

[0121] [α] D (25.0 °C, c = 1.0 in CH2Cl2) = -78.08.

[0122] Example 9

[0123]

[0124] (1S,2R)-N,N-dibenzyl-1-phenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)butan-1-amine

[0125] 1 1H NMR (500 MHz, Chloroform-d) δ 7.41 (d, J = 7.5 Hz, 4H), 7.36 (t, J = 7.5 Hz, 2H), 7.31–7.24 (m, 5H), 7.19 (t, J = 7.5 Hz, 2H), 7.13 (d, J = 7.5 Hz, 2H), 3.97 (d, J = 13.5 Hz, 2H), 3.93 (d, J = 12.0 Hz, 1H), 2.93 (d, J = 13.5 Hz, 2H), 2.01–1.96 (m, 1H), 1.40 (s, 6H), 1.38 (s, 6H), 1.19–1.09 (m, 1H), 1.02–0.97 (m, 1H), 0.79 (t, J = 7.5 Hz, 3H).

[0126] 13 13C NMR (150 MHz, Chloroform-d) δ 163.52, 161.90, 139.77 (d, J = 5.85 Hz), 139.49, 129.16, 127.90, 126.65, 113.75 (d, J = 20.85 Hz), 83.28, 64.35, 54.21, 25.78, 25.45, 22.49, 13.47.

[0127] 11 11B NMR (193 MHz, Chloroform-d) δ 34.27.

[0128] HRMS (ESI-TOF) (m / z): Calcd for C 30 H38 BNO2([M+H] + ), 455.2996, found: 455.2958.

[0129] Mp: 124 - 126 °C

[0130] HPLC analysis of the corresponding alcohol (OD - 3, Hexane / IPA = 95 / 5, 1.0 mL / min, 254 nm) indicated 92% ee: tR (major) = 6.28 min, tR (minor) = 8.03 min.

[0131] [α] D (25.0 °C, c = 1.0 in CH2Cl2) = -45.65.

[0132] Example 10

[0133]

[0134] (1S,2R)-N,N - dibenzyl - 1 - phenyl - 2 - (4,4,5,5 - tetramethyl - 1,3,2 - dioxaborolan - 2 - yl)pentan - 1 - amine

[0135] 1 H NMR (600 MHz, Chloroform - d) δ 7.41 (d, J = 7.2 Hz, 4H), 7.36 (t, J = 7.2 Hz, 2H), 7.29 (t, J = 6.6 Hz, 1H), 7.25 (t, J = 7.2 Hz, 4H), 7.19 (t, J = 7.8 Hz, 2H), 7.12 (d, J = 7.2 Hz, 2H), 3.97 (d, J = 13.8 Hz, 2H), 3.92 (d, J = 12.6 Hz, 1H), 2.93 (d, J = 13.8 Hz, 2H), 2.09–2.05 (m, 1H), 1.39 (s, 6H), 1.37 (s, 6H), 1.29–1.23 (m, 2H), 1.18–1.12 (m, 1H), 0.90–0.86 (m, 1H), 0.72 (t, J = 6.6 Hz, 3H).

[0136] 1313C NMR (150 MHz, Chloroform-d) δ 138.83, 135.65, 128.51, 128.20, 126.82, 126.68, 125.83, 125.51, 82.19, 63.82, 53.20, 30.91, 24.78, 24.46, 21.31, 13.27.

[0137] 11 11B NMR (193 MHz, Chloroform-d) δ 34.36.

[0138] HRMS (ESI-TOF) (m / z): Calcd for C 31 H 40 BNO2 ([M+H] + ), 469.3152, found: 469.3156.

[0139] HPLC analysis of the corresponding alcohol (OD-H, Hexane / IPA = 95 / 5, 1.0 mL / min, 254 nm) indicated 90% ee: tR (major) = 5.11 min, tR (minor) = 6.85 min.

[0140] [α] D (25.0 °C, c = 1.0 in CH2Cl2) = -85.16.

[0141] Example 11

[0142]

[0143] (1S,2R)-N,N-dibenzyl-1-phenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)hexan-1-amine

[0144] 11H NMR (600 MHz, Chloroform-d) δ 7.41 (d, J = 7.8 Hz, 4H), 7.37 (t, J = 7.8 Hz, 2H), 7.28 (t, J = 6.6 Hz, 1H), 7.26 (t, J = 7.2 Hz, 4H), 7.19 (t, J = 7.2 Hz, 2H), 7.13 (d, J = 7.8 Hz, 2H), 3.97 (d, J = 13.8 Hz, 2H), 3.92 (d, J = 12.0 Hz, 1H), 2.93 (d, J = 13.2 Hz, 2H), 2.08–2.04 (m, 1H), 1.40 (s, 6H), 1.38 (s, 6H), 1.21–1.15 (m, 4H), 1.10–1.06 (m, 1H), 0.91–0.86 (m, 1H), 0.73 (t, J = 6.6 Hz, 3H).

[0145] 13 13C NMR (150 MHz, Chloroform-d) δ 139.87, 136.69, 129.54, 129.24, 127.86, 127.71, 126.87, 126.55, 83.21, 64.88, 54.24, 31.44, 29.29, 25.82, 25.53, 22.71, 13.95.

[0146] 11 11B NMR (193 MHz, Chloroform-d) δ 34.10.

[0147] HRMS (ESI-TOF) (m / z): Calcd for C 32 H 42 BNO2 ([M + H] + ), 483.3309, found: 483.3394.

[0148] HPLC analysis of the corresponding alcohol (OD-3, Hexane / IPA = 98 / 2, 1.0 mL / min, 254 nm) indicated 90% ee: tR (major) = 5.79 min, tR (minor) = 6.49 min.

[0149] [α] D (25.0 °C, c = 1.0 in CH2Cl2) = -90.87.

[0150] Example 12

[0151]

[0152] (1S,2R)-N,N-dibenzyl-1-phenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)heptan-1-amine

[0153] Following the General procedure I at a 0.2mmol scale to afford thetittle compound as a colorless oil with 95%yield(94.4mg).

[0154] 1 H NMR(500MHz,Chloroform-d)δ7.41(d,J=7.5Hz,4H),7.36(t,J=7.5Hz,2H),7.30(d,J=7.5Hz,2H),7.26(t,J=7.5Hz,4H),7.19(t,J=7.0Hz,2H),7.12(d,J=7.5Hz,2H),3.97(d,J=13.5Hz,2H),3.92(d,J=12.5Hz,1H),2.92(d,J=13.5Hz,2H),2.09–2.03(m,1H),1.39(s,6H),1.38(s,6H),1.26–1.21(m,2H),1.17–1.12(m,4H),1.05–1.01(m,1H),0.92–0.88(m,1H),0.77(t,J=7.5Hz,3H).

[0155] 13 C NMR(150MHz,Chloroform-d)δ139.88,136.67,129.54,129.25,128.75,128.23,127.87,127.73,126.88,126.57,83.23,64.88,54.23,31.87,29.63,28.91,25.86,25.53,22.51,13.97.

[0156] 11 B NMR(193MHz,Chloroform-d)δ33.77.

[0157] HRMS(ESI-TOF)(m / z):Calcd for C 33 H 44 BNO2([M+H] +), 497.3465, found: 497.3446.

[0158] HPLC analysis of the corresponding alcohol (OD-3, Hexane / IPA = 98 / 2, 1.0 mL / min, 254 nm) indicated 90% ee: tR (major) = 5.78 min, tR (minor) = 6.35 min.

[0159] [α] D (25.0 °C, c = 1.0 in CH2Cl2) = -85.16.

[0160] Example 13

[0161]

[0162] (1S,2R)-N,N-dibenzyl-6-methyl-1-phenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)heptan-1-amine

[0163] 1 1H NMR (500 MHz, Chloroform-d) δ 7.42 (d, J = 7.0 Hz, 4H), 7.37 (t, J = 7.5 Hz, 2H), 7.30 (d, J = 7.0 Hz, 1H), 7.26 (t, J = 7.5 Hz, 4H), 7.19 (t, J = 7.0 Hz, 2H), 7.13 (d, J = 7.0 Hz, 2H), 3.98 (d, J = 14.0 Hz, 2H), 3.92 (d, J = 12.0 Hz, 1H), 2.93 (d, J = 13.5 Hz, 2H), 2.10–2.05 (m, 1H), 1.40 (s, 6H), 1.39 (s, 6H), 1.27–1.23 (m, 2H), 1.16–1.10 (m, 3H), 1.05–1.01 (m, 1H), 0.92–0.88 (m, 1H), 0.76 (d, J = 6.5 Hz, 6H).

[0164] 1313C NMR (150 MHz, Chloroform-d) δ 139.89, 136.72, 129.55, 129.25, 128.75, 128.22, 127.87, 127.74, 126.88, 126.56, 83.23, 64.92, 54.25, 39.06, 29.97, 27.85, 27.04, 25.89, 25.53, 22.60, 22.48.

[0165] 11 11B NMR (193 MHz, Chloroform-d) δ 33.96.

[0166] HRMS (ESI-TOF) (m / z): Calcd for C 34 H 46 BNO2 ([M+H] + ), 511.3622, found: 511.3691.

[0167] Mp: 90 - 92 °C

[0168] HPLC analysis of the corresponding alcohol (OD-H, Hexane / IPA = 95 / 5, 1.0 mL / min, 254 nm) indicated 98% ee: tR (major) = 4.76 min, tR (minor) = 5.31 min.

[0169] [α] D (25.0 °C, c = 1.0 in CH2Cl2) = -83.96.

[0170] Example 14

[0171]

[0172] (1S,2R)-N,N-dibenzyl-1,6-diphenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)hexan-1-amine 1H NMR(500MHz,Chloroform-d)δ7.40(d,J=7.5Hz,4H),7.36(d,J=7.5Hz,2H),7.31(d,J=7.0Hz,1H),7.26(t,J=7.0Hz,4H),7.22–7.18(m,4H),7.12(d,J=7.5Hz,3H),7.05(d,J=7.0Hz,2H),3.96(d,J=13.5Hz,2H),3.91(d,J=12.0Hz,1H),2.92(d,J=13.5Hz,2H),2.50–2.34(m,2H),2.08–2.03(m,1H),1.53–1.46(m,1H),1.42–1.38(m,1H),1.34(s,6H),1.31(s,6H),1.20–1.12(m,3H),0.97–0.92(m,1H).

[0173] 13 C NMR(150MHz,Chloroform-d)δ142.63,139.86,136.69,129.55,129.26,128.42,128.17,127.89,127.79,126.95,126.59,125.50,83.25,64.90,54.26,35.76,31.39,29.60,28.74,25.84,25.49.

[0174] 11 B NMR(193MHz,Chloroform-d)δ34.00.

[0175] HRMS(ESI-TOF)(m / z):Calcd for C 38 H 46 BNO2([M+H] + ),559.3622,found:559.3616.

[0176] HPLC analysis of the corresponding alcohol(OD-H,Hexane / IPA=95 / 5,1.0mL / min,254nm)indicated 94%ee:tR(major)=7.57min,tR(minor)=16.55min.

[0177] [α] D (25.0℃,c=1.0in CH2Cl2)=-9.13.

[0178] Example 15

[0179]

[0180] (1S,2R)-N,N-dibenzyl-5-cyclohexyl-1-phenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pentan-1-amine

[0181] 1 H NMR(500MHz,Chloroform-d)δ7.42(d,J=8.0Hz,4H),7.37(t,J=7.5Hz,2H),7.31(d,J=7.0Hz,1H),7.26(t,J=7.5Hz,4H),7.20(t,J=7.0Hz,2H),7.13(d,J=7.5Hz,2H),3.97(d,J=13.5Hz,2H),3.92(d,J=12.0Hz,1H),2.92(d,J=14.0Hz,2H),2.09–2.04(m,1H),1.62–1.55(m,5H),1.40(s,6H),1.39(s,6H),1.27–1.23(m,2H),1.16–1.09(m,5H),1.04–1.00(m,1H),0.90–0.85(m,2H),0.77–0.73(m,2H).

[0182] 13 C NMR(150MHz,Chloroform-d)δ139.88,136.71,129.55,129.23,128.75,128.74,128.20,127.85,127.71,126.85,126.54,83.20,64.89,54.23,37.46,37.43,33.39,33.19,29.91,26.73,26.42,26.40,26.36,25.86,25.52.

[0183] 11 B NMR(193MHz,Chloroform-d)δ34.21.

[0184] HRMS(ESI-TOF)(m / z):Calcd for C 37 H 50 BNO2([M+H] + ),551.3935,found:551.3959.

[0185] Mp: 77 - 79 °C

[0186] HPLC analysis of the corresponding alcohol (IC, Hexane / IPA = 95 / 5, 1.0 mL / min, 254 nm) indicated 90% ee: tR (major) = 5.14 min, tR (minor) = 6.15 min.

[0187] [α] D (25.0 °C, c = 1.0 in CH2Cl2) = -15.52.

[0188] Example 16

[0189]

[0190] (1S,2R)-N,N-dibenzyl-5-methoxy-1-phenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pentan-1-amine

[0191] 1 H NMR (500 MHz, Chloroform-d) δ 7.41 (d, J = 7.5 Hz, 4H), 7.37 (t, J = 7.5 Hz, 2H), 7.30 (d, J = 7.0 Hz, 1H), 7.26 (t, J = 7.5 Hz, 4H), 7.19 (t, J = 7.0 Hz, 2H), 7.12 (d, J = 7.5 Hz, 2H), 3.96 (d, J = 13.5 Hz, 2H), 3.92 (d, J = 12.5 Hz, 1H), 3.19 (s, 3H), 3.18–3.11 (m, 2H), 2.92 (d, J = 13.5 Hz, 2H), 2.10–2.04 (m, 1H), 1.56–1.48 (m, 1H), 1.46–1.41 (m, 1H), 1.39 (s, 6H), 1.38 (s, 6H), 1.19–1.13 (m, 1H), 0.99–0.93 (m, 1H).

[0192] 13 C NMR (150 MHz, Chloroform-d) δ 139.77, 136.40, 129.52, 129.22, 127.88, 127.79, 126.97, 126.59, 83.33, 72.89, 64.74, 58.33, 54.21, 28.93, 25.94, 25.85, 25.52.

[0193] 11 11B NMR(193MHz,Chloroform-d)δ33.98.

[0194] HRMS(ESI-TOF)(m / z):Calcd for C 32 H 42 BNO3([M+H] + ),499.3258,found:499.3229.

[0195] Mp:86 - 88 °C

[0196] HPLC analysis of the corresponding alcohol(IA - 3,Hexane / IPA=95 / 5,1.0 mL / min,254 nm)indicated 94%ee:tR(major)=9.35 min,tR(minor)=13.03 min.

[0197] [α] D (25.0 °C,c=1.0 in CH2Cl2)=13.242.

[0198] Example 17

[0199]

[0200] 4 - ((3R,4S)-4-(dibenzylamino)-4-phenyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)butyl)piperidine-1-carboxylate 1 1H NMR(500 MHz,Chloroform-d)δ7.41(d,J=7.8 Hz,4H),7.37(t,J=7.2 Hz,2H),7.31(d,J=7.2 Hz,1H),7.26(t,J=7.2 Hz,4H),7.20(t,J=7.2 Hz,2H),7.12(d,J=7.8 Hz,2H),3.98–3.91(m,5H),2.93(d,J=13.2 Hz,2H),2.56–2.53(m,2H),2.04–2.00(m,1H),1.42(s,9H),1.39(s,6H),1.38(s,6H),1.21–1.10(m,5H),0.97–0.90(m,2H),0.88–0.81(m,2H).

[0201] 13 C NMR (150 MHz, Chloroform-d) δ 154.87, 139.79, 136.59, 129.47, 129.23, 127.89, 127.79, 126.99, 126.60, 83.28, 79.07, 64.82, 54.26, 36.07, 35.88, 32.55, 31.65, 28.48, 26.94, 26.66, 25.81, 25.58.

[0202] 11 B NMR (193 MHz, Chloroform-d) δ 34.00.

[0203] HRMS (ESI-TOF) (m / z): Calcd for C 40 H 55 BN2O4 ([M + H] + ), 638.4255, found: 638.4295.

[0204] HPLC analysis of the corresponding alcohol (OD-3, Hexane / IPA = 98 / 2, 1.0 mL / min, 254 nm) indicated 90% ee: tR (major) = 18.48 min, tR (minor) = 23.61 min.

[0205] [α] D (25.0 °C, c = 1.0 in CH2Cl2) = -41.32.

[0206] Example 18

[0207]

[0208] (1S,2R)-N-benzyl-1-phenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-N-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl)butan-1-amine 1H NMR(500MHz,Chloroform-d)7.71(s,1H),7.66(t,J=8.2Hz,2H),7.41(d,J=7.5Hz,2H),7.37(t,J=7.5Hz,2H),7.31–7.25(m,4H),7.21–7.18(m,1H),7.14(d,J=7.5Hz,2H),4.14(d,J=13.2Hz,1H),3.92(d,J=12.5Hz,1H),3.79(d,J=14.0Hz,1H),3.02(d,J=13.0Hz,1H),2.90(d,J=14.0Hz,1H),2.02–1.97(m,1H),1.41(s,6H),1.39(s,6H),1.32(s,12H),1.17–1.12(m,1H),1.02–0.95(m,1H),0.79(t,J=7.5Hz,3H).

[0209] 13 C NMR(150MHz,Chloroform-d)δ139.85,139.12,136.70,135.63,133.17,132.53,129.59,129.20,127.85,127.70,127.33,126.87,126.48,83.59,83.24,64.93,54.35,54.02,25.91,25.50,24.95,24.88,22.70,13.58.

[0210] 11 B NMR(193MHz,Chloroform-d)δ33.02,29.99.

[0211] HRMS(ESI-TOF)(m / z):Calcd for C 36 H 49 B2NO4([M+H] + ),581.3848,found:581.3873.

[0212] HPLC analysis of the corresponding alcohol(OD-3,Hexane / IPA=98 / 2,1.0mL / min,254nm)indicated 94%ee:tR(major)=13.54min,tR(minor)=15.33min.

[0213] [α] D(25.0 °C, c = 1.0 in CH2Cl2) = 10.96.

[0214] Example 19

[0215]

[0216] (1S,2R)-N-benzyl-1-phenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-N-(4-(trifluoromethyl)benzyl)butan-1-amine 1 H NMR (500 MHz, Chloroform-d) δ 7.55–7.51 (m, 4H), 7.41–7.37 (m, 4H), 7.32 (d, J = 7.0 Hz, 1H), 7.27 (t, J = 7.5 Hz, 2H), 7.20 (t, J = 7.5 Hz, 1H), 7.12 (d, J = 7.5 Hz, 2H), 3.99–3.94 (m, 2H), 3.91 (d, J = 12.5 Hz, 1H), 3.02 (d, J = 14.0 Hz, 1H), 2.98 (d, J = 13.5 Hz, 1H), 2.02–1.97 (m, 1H), 1.41 (s, 6H), 1.39 (s, 6H), 1.18–1.12 (m, 1H), 1.06–1.00 (m, 1H), 0.81 (t, J = 7.0 Hz, 3H).

[0217] 13 C NMR (150 MHz, Chloroform-d) δ 144.28, 139.46, 136.46, 129.44, 129.30, 129.19, 127.99, 127.90, 127.12, 126.79, 124.83 (q, J = 3.8 Hz), 124.42 (q, J = 271.8 Hz), 83.32, 65.07, 54.35, 54.04, 25.82, 25.54, 22.63, 13.52.

[0218] 19 F NMR (565 MHz, Chloroform-d) δ -62.24.

[0219] 11 B NMR (193 MHz, Chloroform-d) δ 36.22.

[0220] HRMS (ESI-TOF) (m / z): Calcd for C 31 H37 BF3NO2([M+H] + ), 523.2869, found: 523.2872.

[0221] Mp: 82 - 84 °C

[0222] HPLC analysis of the corresponding alcohol (OD-H, Hexane / IPA = 95 / 5, 1.0 mL / min, 254 nm) indicated 90% ee: tR (major) = 5.12 min, tR (minor) = 8.60 min.

[0223] [α] D (25.0 °C, c = 1.0 in CH2Cl2) = -2.28.

[0224] Example 20

[0225]

[0226] (1S,2R)-N-benzyl-N-methyl-1-phenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)butan-1-amine 1 H NMR (500 MHz, Chloroform-d) δ 7.35 (t, J = 8.0 Hz, 4H), 7.29–7.24 (m, 3H), 7.21–7.18 (m, 3H), 3.83 (d, J = 12.0 Hz, 1H), 3.45 (d, J = 13.0 Hz, 1H), 3.02 (d, J = 12.5 Hz, 1H), 2.06 (s, 3H), 1.96–1.90 (m, 1H), 1.33 (s, 6H), 1.32 (s, 6H), 1.29–1.24 (m, 1H), 1.14–1.08 (m, 1H), 0.86 (t, J = 7.0 Hz, 3H).

[0227] 13 C NMR (150 MHz, Chloroform-d) δ 139.78, 136.43, 129.60, 129.29, 127.75, 126.96, 126.65, 83.08, 70.46, 58.55, 37.79, 25.02, 24.96, 22.04, 13.92.

[0228] 1111B NMR (193 MHz, Chloroform-d) δ 35.68.

[0229] HRMS (ESI-TOF) (m / z): Calcd for C 24 H 34 BNO2 ([M+H] + ), 379.2683, found: 379.2668.

[0230] HPLC analysis of the corresponding alcohol (OD-H, Hexane / IPA = 95 / 5, 1.0 mL / min, 254 nm) indicated 97% ee: tR (minor) = 5.09 min, tR (major) = 5.54 min.

[0231] [α] D (25.0 °C, c = 1.0 in CH2Cl2) = 24.88.

[0232] Example 21

[0233]

[0234] 1-((1S,2R)-1-phenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)butyl)piperidine 1 1H NMR (500 MHz, Chloroform-d) δ 7.31 (t, J = 7.0 Hz, 2H), 7.24 (t, J = 7.0 Hz, 1H), 7.11 (d, J = 7.0 Hz, 2H), 3.59 (d, J = 12.5 Hz, 1H), 2.46 (s, 2H), 2.14 (s, 2H), 1.89–1.84 (m, 1H), 1.54–1.45 (m, 1H), 1.35 (s, 12H), 1.25–1.20 (m, 1H), 1.08–1.02 (m, 1H), 0.83 (t, J = 7.0 Hz, 3H).

[0235] 13 13C NMR (150 MHz, Chloroform-d) δ 136.45, 129.17, 127.46, 126.71, 82.78, 72.36, 26.15, 25.55, 24.77, 24.62, 21.97, 13.96.

[0236] 1111B NMR (193 MHz, Chloroform-d) δ 33.01.

[0237] HRMS (ESI-TOF) (m / z): Calcd for C 21 H 34 BNO2 ([M+H] + ), 343.2683, found: 343.2659.

[0238] Mp: 94 - 96 °C

[0239] HPLC analysis of the corresponding alcohol (AD-3, Hexane / IPA = 99.5 / 0.5, 1.0 mL / min, 210 nm) indicated 98% ee: tR (minor) = 7.58 min, tR (major) = 8.13 min.

[0240] [α] D (25.0 °C, c = 1.0 in CH2Cl2) = 17.81.

[0241] Example 22

[0242]

[0243] 4-((1S,2R)-1-phenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)butyl)morpholine 1 1H NMR (500 MHz, Chloroform-d) δ 7.33 (t, J = 7.0 Hz, 2H), 7.27–7.24 (m, 1H), 7.11 (d, J = 7.5 Hz, 2H), 3.67–3.58 (m, 5H), 2.53 (s, 2H), 2.26 (s, 2H), 1.87–1.81 (m, 1H), 1.35 (s, 12H), 1.27–1.21 (m, 1H), 1.12–1.06 (m, 1H), 0.84 (t, J = 7.5 Hz, 3H).

[0244] 13 13C NMR (150 MHz, Chloroform-d) δ 135.77, 129.12, 127.76, 127.12, 82.95, 71.88, 67.09, 25.50, 24.86, 21.76, 13.89.

[0245] 1111B NMR (193 MHz, Chloroform-d) δ 33.54.

[0246] HRMS (ESI-TOF) (m / z): Calcd for C 20 H 32 BNO3 ([M+H] + ), 345.2475, found: 345.2449.

[0247] HPLC analysis of the corresponding alcohol (OD-3, Hexane / IPA = 96 / 4, 1.0 mL / min, 254 nm) indicated 95% ee: tR (major) = 8.13 min, tR (minor) = 12.21 min.

[0248] [α] D (25.0 °C, c = 1.0 in CH2Cl2) = 27.84.

[0249] Example 23

[0250]

[0251] N-butyl-N-((1S,2R)-1-phenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)butyl)pent-4-en-1-amine 1 1H NMR (500 MHz, Chloroform-d) δ 7.30 (t, J = 7.0 Hz, 2H), 7.23 (t, J = 7.5 Hz, 1H), 7.14 (d, J = 7.5 Hz, 2H), 5.87–5.79 (m, 1H), 5.00 (d, J = 18.5 Hz, 1H), 4.93 (d, J = 10.0 Hz, 1H), 3.79 (d, J = 12.5 Hz, 1H), 2.60–2.51 (m, 2H), 2.10–1.96 (m, 2H), 1.93–1.87 (m, 2H), 1.85–1.79 (m, 1H), 1.64–1.54 (m, 2H), 1.53–1.42 (m, 2H), 1.31 (s, 12H), 1.28–1.17 (m, 3H), 1.07–1.01 (m, 1H), 0.90 (t, J = 7.5 Hz, 3H), 0.82 (t, J = 7.5 Hz, 3H).

[0252] 1313C NMR (150 MHz, Chloroform-d) δ 139.04, 137.59, 129.17, 127.61, 126.64, 114.13, 82.89, 66.33, 50.37, 50.15, 31.99, 30.89, 27.92, 25.38, 25.14, 22.27, 20.95, 14.24, 13.87.

[0253] 11 11B NMR (193 MHz, Chloroform-d) δ 33.74.

[0254] HRMS (ESI-TOF) (m / z): Calcd for C 25 H 42 BNO2 ([M + H] + ), 399.3309, found: 399.3348.

[0255] HPLC analysis of the corresponding alcohol (OD-3, Hexane / IPA = 99.9 / 0.1, 1.0 mL / min, 254 nm) indicated 91% ee: tR (major) = 3.85 min, tR (minor) = 4.30 min.

[0256] [α] D (25.0 °C, c = 1.0 in CH2Cl2) = -27.63.

[0257] Example 24

[0258]

[0259] (1R,2S)-N,N-dibenzyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(3-((((R)-2,5,7,8-tetramethyl-2-((4R,8R)-4,8,12-trimethyltridecyl)chroman-6-yl)oxy)methyl)phenyl)butan-1-amine

[0260] 1H NMR(500MHz,Chloroform-d)δ7.44–7.41(m,6H),7.27–7.24(m,4H),7.22–7.19(m,3H),7.14(d,J=7.0Hz,1H),4.69(s,2H),3.97(t,J=13.0Hz,3H),2.95(d,J=13.5Hz,2H),2.60(t,J=6.5Hz,2H),2.24(s,3H),2.19(s,3H),2.11(s,3H),2.05–1.99(m,1H),1.85–1.73(m,H),1.56–1.52(m,3H),1.41–139(m,16H),1.28–1.23(m,10H),1.16–1.11(m,4H),1.08–1.04(m,4H),0.87–0.84(m,12H),0.80(t,J=7.5Hz,3H).

[0261] 13 C NMR(150MHz,Chloroform-d)δ148.18,147.94,139.84,137.31,136.89,129.28,127.87,126.75,126.58,125.98,122.95,117.60,83.26,75.15,74.83,64.62,54.25,40.13,39.40,37.52,37.49,37.46,37.32,32.83,32.74,31.33,28.01,25.84,25.54,24.83,24.48,23.93,22.76,22.69,22.66,21.07,20.73,19.79,19.70,13.61,12.99,12.12,11.88.

[0262] 11 B NMR(193MHz,Chloroform-d)δ33.28.

[0263] HRMS(ESI-TOF)(m / z):Calcd for C 60 H 88 BNO4([M+H]+),897.6806,found:897.6816.

[0264] [α] D (25.0℃,c=1.0in CH2Cl2)=6.95.

[0265] It should be noted that when the present invention involves a numerical range, it should be understood that the two endpoints of each numerical range and any value between the two endpoints can be selected. Since the steps and methods used are the same as those in the embodiments, in order to avoid redundancy, the present invention describes a preferred embodiment. Although the preferred embodiments of the present invention have been described, those skilled in the art may make additional changes and modifications to these embodiments once they know the basic creative concept. Therefore, the attached claims are intended to be interpreted as including the preferred embodiments and all changes and modifications that fall within the scope of the present invention.

[0266] Obviously, those skilled in the art can make various changes and modifications to the present invention without departing from the spirit and scope of the present invention. Thus, if these modifications and variations of the present invention fall within the scope of the claims of the present invention and their equivalents, the present invention is also intended to include these modifications and variations.

Claims

1. A Co-Cu co-catalyzed enantioselective remote boroamination reaction method for non-activated olefins, characterized in that: The following steps are involved: Under a protective atmosphere, LiO t Bu is the substrate, CuCl is the catalyst, (S,S)- i Pr-phosferrox is a chiral ligand, and the mixed reaction is activated to obtain a copper catalytic system; In tetrahydrofuran solvent, LiO t Bu and 4-phenyl-1-butene derivatives are substrates, B2pin2 is a reducing agent, CoBr2 is a catalyst, (S,S)-Ph-BPE is a chiral ligand, and the cobalt catalytic system is obtained by mixed reaction activation; The copper catalytic system is added to the cobalt catalytic system, and a derivative of N,N-dialkylhydroxylamine is added to the mixed reaction system to introduce nitrogen functional groups. CoBr2 is reacted with LiO t Under the action of Bu and B2pin2, divalent Co is reduced to generate the first intermediate Co-Bpin, which undergoes migration insertion and β-H elimination with a 4-phenyl-1-butene derivative to obtain a second intermediate Co-H, which undergoes continuous migration insertion and β-H elimination with a 4-phenyl-1-butene derivative to obtain a trans olefin of a single configuration, completing the Co catalytic cycle; then the trans olefin of a single configuration enters the Cu catalytic system for cyclic catalysis, and the trans olefin of a single configuration undergoes selective migration insertion with the Cu-Bpin intermediate in the copper catalytic system to obtain a fourth intermediate, and then the fourth intermediate undergoes oxidative addition reduction elimination with a derivative of N,N-dialkylhydroxylamine to obtain the target product, thereby realizing the enantioselective remote boroamination reaction of non-activated olefins.

2. The Co-Cu combined catalytic non-activated olefin enantioselective distal boroamination reaction method according to claim 1, characterized in that: In the copper catalytic system, CuCl, (S,S)- i Pr-phosferrox and LiO t The molar ratio of Bu is 1:1.2:

36.

3. The Co-Cu combined catalytic non-activated olefin enantioselective remote boroamination reaction method according to claim 1, characterized in that: LiO t The usage ratio of Bu to tetrahydrofuran is 0.36mmol:0.5mL.

4. The Co-Cu combined catalytic non-activated olefin enantioselective remote boroamination reaction method according to claim 1, characterized in that: In the cobalt catalytic system, the molar ratio of CoBr2, (S,S)-Ph-BPE, B2pin2 and 4-phenyl-1-butene derivative is 1:1.2:40:

20.

5. The Co-Cu combined catalytic non-activated olefin enantioselective remote boroamination reaction method according to claim 1, characterized in that: LiO t The usage ratio of Bu, 4-phenyl-1-butene derivative and tetrahydrofuran is 0.04 mol:0.2 mmol:0.5 mL.

6. The Co-Cu combined catalytic non-activated olefin enantioselective remote boroamination reaction method according to claim 1, characterized in that: The molar ratio of the derivative of N,N-dialkylhydroxylamine to CuCl is 0.3:0.01, and the molar ratio of the derivative of N,N-dialkylhydroxylamine to CoBr2 is 0.3:0.

01.

7. The Co-Cu combined catalytic non-activated olefin enantioselective remote boroamination reaction method according to claim 1, characterized in that: The volume ratio of the copper catalyst system to the cobalt catalyst system is 1:

1.

8. The Co-Cu combined catalytic non-activated olefin enantioselective remote boroamination reaction method according to claim 1, characterized in that: The activation time of the copper catalytic system and the cobalt catalytic system is 30 minutes, and the reaction temperature is 23°C to 28°C.

9. The Co-Cu combined catalytic non-activated olefin enantioselective remote boroamination reaction method according to claim 1, characterized in that: The reaction temperature of the Cu catalytic system and the Co catalytic system is 23°C to 40°C, and the reaction time is 36h.

10. The Co-Cu combined catalytic non-activated olefin enantioselective remote boroamination reaction method according to claim 1, characterized in that: After the reaction is completed, the reaction is quenched with water, extracted, concentrated in vacuo, and the residue is purified by neutral Al2O3 or amino silica gel column chromatography.

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