Chiral phase transfer catalyst, its preparation method and application

Abstract

The application provides a chiral phase transfer catalyst as well as a preparation method and application thereof, belongs to the technical field of organic chemistry, and has a wide market application prospect in the application of the chiral phase transfer catalyst to Michael addition [3+3] asymmetric cyclization reaction and asymmetric catalysis. Moreover, the preparation method of the chiral phase transfer catalyst has strong operability, a novel synthesis route and high yield.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of pharmaceutical chemistry, in particular to a phase transfer catalyst and a preparation method and application thereof. BACKGROUND

[0002] Chiral phase transfer catalyst is a kind of small molecule catalyst with advantages, and is various, can efficiently catalyze multiple types of reactions, generally involves simple experimental procedures of PTC, mild reaction conditions, safety, relatively cheap reagents and solvents and is environment-friendly; on the other hand, the experiment involved is easy to transfer to large-scale synthesis. The chemical reaction mediated by chiral phase transfer catalyst is one of the research hotspots of current organic chemists, and the chiral phase transfer catalyst is widely accepted as one of the most powerful reagents in industry. With the continuous deepening of research, it is more important to research new chiral phase transfer catalysts.

[0003] How to design and prepare new chiral phase transfer catalysts with high yield is the research difficulty and key point at present. SUMMARY

[0004] In view of the problems in the prior art, the present application provides a new chiral phase transfer catalyst and a preparation method and application thereof.

[0005] The technical scheme adopted by the present application to solve the technical problems is that the chiral phase transfer catalyst has the following structure:

[0006]

[0007] Meanwhile, the present application also provides a method for preparing the chiral phase transfer catalyst, which comprises: sequentially adding 1 eq of cinchonine 1, toluene and 1.4 eq of 4-methylbenzyl bromide 2 into a sealed tube, refluxing the reaction solution for 4 hours, filtering after cooling, and drying the solid after washing with toluene to obtain the target product 3, i.e. the chiral phase transfer catalyst, and the reaction formula is as follows:

[0008]

[0009] Further, the present application also provides the application of the chiral phase transfer catalyst in mediating asymmetric reaction.

[0010] Still further, the asymmetric reaction is Michael addition [3+3] asymmetric cyclization reaction.

[0011] That is, the chiral phase transfer catalyst provided by the present application can be used to mediate Michael addition [3+3] asymmetric cyclization reaction.

[0012] The application provides a novel chiral phase transfer catalyst which can well mediate Michael addition [3+3] asymmetric cyclization reaction and obtain optically active reaction products, and has wide market application prospect due to strong operability, novel synthesis route and high yield. BRIEF DESCRIPTION OF DRAWINGS

[0013] Figure 1 Single crystal diagram of product 6e in Example 5. DETAILED DESCRIPTION

[0014] In order to make the technical means, creative features, purposes and effects of the application easy to understand, the application is further described below in combination with specific embodiments. However, it should not be understood that the scope of the above-mentioned subject matter of the application is limited to the following examples. According to the above-mentioned content of the application, according to the ordinary technical knowledge and conventional means in the art, other various forms of modification, replacement or change can be made without departing from the above-mentioned basic technical idea of the application. Any technology achieved based on the above-mentioned content of the application belongs to the scope of the application.

[0015] Definitions of terms used in the application: unless otherwise specified, the initial definition of a group or term provided herein is applicable to the group or term throughout the specification; for the terms not specifically defined herein, the meanings should be given to them according to the disclosure and the context, which can be given to them by the person skilled in the art.

[0016] Unless specifically indicated, the reagents and test equipment used in the application are all conventional commercially available reagents and equipment.

[0017] Example 1

[0018] First, the chiral phase transfer catalyst (1S,2S,4S,5R)-2((S)-hydroxyquinoline-4-methyl)-1-(4-methoxycarbonyl) benzyl)-5-vinyl quinuclidine-1-ium bromide is prepared, and the specific steps are as follows:

[0019] Into a clean sealed tube, add octenidine 1 (1 eq), toluene and 4-methylbenzyl bromide 2 (1.4 eq) in sequence, reflux the reaction solution for 4 hours, after the reaction is completed, filter after cooling, wash the solid with toluene and dry to obtain the chiral phase transfer catalyst 3, i.e. (1S,2S,4S,5R)-2((S)-hydroxyquinoline-4-methyl)-1-(4-methoxycarbonyl) benzyl)-5-vinyl quinuclidine-1-ium bromide, and the specific reaction formula is as follows:

[0020]

[0021] The structure of chiral phase transfer catalyst 3 was characterized by 1 H NMR, 13 C NMR:

[0022] Bromide salt of (1S,2S,4S,5R)-2((S)-hydroxyquinolin-4-ylmethyl)-1-(4- methoxycarbonyl)benzyl)-5-vinylquinuclidin-1-ium

[0023]

[0024] Pale yellow solid, yield 75%

[0025] 1 H NMR (600 MHz, CDC13) δ (ppm): 8.80 (d, J = 4.2 Hz, 1H), 8.25 (d, J = 8.4 Hz, 1H), 7.83 (d, J = 4.8 Hz, 1H), 7.70 - 7.64 (m, 3H), 7.47 (d, J = 8.4 Hz, 1H), 6.96 - 6.88 (m, 2H), 6.51 (d, J = 6.0 Hz, 1H), 6.48 - 6.43 (m, 1H), 6.31 (d, J = 11.4 Hz, 1H), 5.83 - 5.76 (m, 1H), 5.49 (d, J = 11.4 Hz, 1H), 5.22 (d, J = 10.2 Hz, 1H), 5.15 (d, J = 17.4 Hz, 1H), 4.46 (t, J = 9.6 Hz, 1H), 4.22 - 4.11 (m, 2H), 3.94 (s, 3H), 3.16 (t, J = 11.4 Hz, 1H), 2.70 - 2.62 (m, 1H), 2.26 - 2.20 (m, 1H), 2.08 - 2.01 (m, 1H), 1.78 - 1.62 (m, 3H), 0.87 - 0.76 (m, 1H), 0.74 - 0.66 (m, 1H).

[0026] 13 C NMR (151 MHz, CDC13) δ (ppm): 165.8, 149.3, 146.8, 144.0, 134.9, 134.1, 131.6, 131.4, 129.5, 129.4, 128.1, 127.0, 123.2, 123.0, 119.6, 118.2, 66.8, 65.6, 60.4, 56.3, 53.8, 52.4, 37.9, 27.0, 23.6, 21.8.

[0027] HRMS (ESI-TOF) m / z: [M + Na] + Calcd for C 28 H 19 NO2SNa + 443.2330; Found 443.2327.

[0028] The catalytic effect of the chiral phase-transfer catalyst 3 is further illustrated by the application of the catalyst to mediate the Michael addition [3+3] asymmetric cyclization reaction.

[0029] Michael addition [3+3] asymmetric cyclization reaction mediated by the chiral phase-transfer catalyst 3

[0030] The chiral phase-transfer catalyst prepared in this example was used to catalyze the reaction of the 2-benzoylbenzothiazole derivative activated by base with the N-acylbenzotriazole compound, and the [3+3] asymmetric cyclization product 6 was successfully obtained, as shown in the following reaction formula:

[0031]

[0032] Test operation: 0.1 mmol of compound 4, 0.2 mmol of compound 5, 0.02 mmol of C3, 0.06 mmol of K3PO4 and 1.0 mL of CHCl3 were added into a reaction test tube, respectively, and reacted at 0°C for 36 hours. After the reaction was completed as detected by thin layer chromatography, compound 6 was obtained by column chromatography purification. The enantiomeric ratio er value was determined by chiral ultra-high performance liquid chromatography.

[0033] The product of this example is 6a, which was characterized by 1 H NMR, 13 C NMR:

[0034] Product 6a

[0035] (R)-4-(4-Fluorobenzoyl)-3-phenyl-2,3-dihydro-1H-benzo[4,5]thiazolo[3,2-a]pyridin-1-one

[0036]

[0037] Yellow solid, 97% yield.

[0038] 1H NMR (600MHz, CDCl3) δ (ppm): 8.46 (d, J = 7.2Hz, 1H), 7.61 (dd, J = 7.8, 1.2Hz, 1H), 7.38 (d, J = 7.8Hz, 1H), 7.36–7.32 (m, 1H), 7.32–7.24 (m ,5H),7.10(d,J=7.2Hz,2H),6.97–6.93(m,2H),4.31(dd,J=6.6,1.8Hz,1H),3.27(dd,J=15.6,7.2Hz,1H),3.05(dd,J=16.2,2.4Hz,1H).

[0039] 13 C NMR (151MHz, CDCl3) δ (ppm): 189.9, 167.7, 163.8 (CF, 1 J C-F =250.1Hz),156.6,140.6,136.0,135.4(CF, 3 J C-F =4.3Hz),129.5,129.4,127.72,127.68,127.1,126.7,125.9,122.0,117.6,115.1(CF, 2 J C-F =21.7Hz), 107.5, 41.5, 38.7.

[0040] HRMS(ESI-TOF)m / z:[M+Na] + Calcd for C 24 H 16 FNO2SNa + 424.0778; Found424.0781.

[0041] Examples 2-12 show the synthesis of different [3+3] asymmetric cyclization products 6 by selecting different compounds 4 and 5 under the catalysis of the chiral phase transfer catalyst of the present invention, as shown in Table 1.

[0042] Table 1. Comparison of data on products synthesized from different compounds.

[0043]

[0044]

[0045] Example 2

[0046] Product 6b

[0047] (R)-4-(2-bromobenzoyl)-3-phenyl-2,3-dihydro-1 H-benzo[4,5]thiazolo[3,2- a]pyridin-1-one

[0048]

[0049] Yellow solid, 87% yield.

[0050] 1 H NMR (600 MHz, CDC13) δ (ppm): 8.51 (d, J = 7.8 Hz, 1H), 7.61 (dd, J = 7.2, 1.2 Hz, 1H), 7,54 (d, J = 7.8 Hz, 1H), 7.39 (t, J = 7.8 Hz, 1H), 7.34 (t, J = 7.2 Hz, 1H), 7.21 - 7.04 (m, 5H), 6.87 - 6.67 (m, 3H), 4.01 (d, J = 6.6 Hz, 1H), 3.40 (dd, J = 15.6, 7.2 Hz, 1H), 3.03 (dd, J = 15.6, 1.8 Hz, 1H).

[0051] 13 C NMR (151 MHz, CDC13) δ (ppm): 190.4, 167.7, 155.6, 140.8, 136.0, 132.4, 130.2, 128.9, 127.7, 127.4, 127.3, 127.13, 127.06, 126.5, 125.9, 122.0, 119.1, 118.3, 117.4, 107.3, 41.1, 38.7.

[0052] HRMS (ESI-TOF) m / z: [M + Na] Calcd for C + Calcd for C 24 H 16 79 BrNO2SNa + 483.9978, C 24 H 16 81 BrNO2SNa + 485.9957; Found 483.9981, 485.9962.

[0053] Example 3

[0054] Product 6c

[0055] (R)-4-(2-bromobenzoyl)-3-phenyl-2,3-dihydro-1 H-benzo[4,5]thiazolo[3,2- a]pyridin-1-one

[0056] (R)-4-(2-bromobenzoyl)-3-phenyl-2,3-dihydro-1 H-benzo[4,5]thiazolo[3,2- a]pyridin-1-one

[0057] Yellow solid, 84% yield.

[0058] 1 H NMR (600 MHz, CDC13) δ (ppm): 8.51 (d, J = 7.2 Hz, 1H), 7.60 (dd, J = 7.8, 1.2 Hz, 1H), 7.39 (t, J = 7.8 Hz, 1H), 7.34 (t, J = 7.2 Hz, 1H), 7.23 (t, J = 7.2 Hz, 1H), 7.18 - 7.14 (m, 3H), 7.11 (d, J = 7.8 Hz, 1H), 7.04 (t, J = 7.8 Hz, 1H), 6.86 - 6.81 (m, 3H), 4.03 (dd, J = 7.8, 2.4 Hz, 1H), 3.31 (dd, J = 16.2, 7.8 Hz, 1H), 2.99 (dd, J = 16.2, 2.4 Hz, 1H), 2.00 (s, 3H).

[0059] 13 C NMR (151 MHz, CDC13) δ (ppm): 193.6, 167.8, 154.9, 141.1, 139.3, 136.0, 134.7, 130.4, 128.9, 127.5, 127.4, 127.0, 126.5, 125.9, 125.4, 125.0, 121.9, 117.4, 108.2, 41.1, 38.8, 18.8.

[0060] HRMS (ESI-TOF) m / z: [M + Na] Calcd for C + Calcd for C 25 H 19 NO2SNa + 420.1029; Found 420.1037.

[0061] Example 4

[0062] Product 6d

[0063] (R)-4-benzoyl-7-chloro-3-phenyl-2,3-dihydro-lH-benzo[4,5]thiazolo[3,2-a]pyridin-l-one

[0064]

[0065] (R)-4-benzoyl-7-chloro-3-phenyl-2,3-dihydro-lH-benzo[4,5]thiazolo[3,2-a]pyridin-l-one

[0066] Yellow solid, 96% yield.

[0067] 1 H NMR (600 MHz, CDC13) δ (ppm): 8.37 (d, J = 8.4 Hz, 1H), 7.56 (d, J = 1.8 Hz, 1H), 7.42 - 7.37 (m, 1H), 7.32 - 7.23 (m, 8H), 7.08 (d, J = 6.6 Hz, 2H), 4.35 (dd, J = 7.2, 3.0 Hz, 1H), 3.27 (dd, J = 15.6, 6.6 Hz, 1H), 3.04 (dd, J = 16.2, 3.0 Hz, 1H).

[0068] 13 C NMR (151 MHz, CDC13) δ (ppm): 191.3, 167.6, 155.6, 140.5, 139.0, 134.6, 131.4, 130.4, 129.8, 129.4, 128.1, 127.6, 127.1, 127.0, 126.7, 121.7, 118.3, 108.0, 41.2, 38.5.

[0069] HRMS (ESI-TOF) m / z: [M + Na] Calcd for C + Calcd for C 24 H 16 35 ClNO2SNa + 440.0483, C 24 H 16 37 ClNO2SNa + 442.0453; Found 440.0487, 442.0463.

[0070] Example 5

[0071] Product 6e

[0072] (R)-4-benzoyl-3-phenyl-2,3-dihydro-lH-benzo[4,5]thiazolo[3,2-a]pyridin-l-one

[0073]

[0074] Yellow solid, 99% yield.

[0075] 1H NMR (600MHz, CDCl3) δ (ppm): 8.46 (d, J = 7.2Hz, 1H), 7.61 (dd, J = 7.8, 1.2Hz, 1H), 7.38 (d, J = 7.8Hz, 1H), 7.36–7.32 (m, 1H), 7.32–7.24 (m ,5H),7.10(d,J=7.2Hz,2H),6.97–6.93(m,2H),4.31(dd,J=6.6,1.8Hz,1H),3.27(dd,J=15.6,7.2Hz,1H),3.05(dd,J=16.2,2.4Hz,1H).

[0076] 13 C NMR (151MHz, CDCl3) δ (ppm): 189.9, 167.7, 163.8 (CF, 1 J C-F =250.1Hz),156.6,140.6,136.0,135.4(CF, 3 J C-F =4.3Hz),129.5,129.4,127.72,127.68,127.1,126.7,125.9,122.0,117.6,115.1(CF, 2 J C-F =21.7Hz), 107.5, 41.5, 38.7.

[0077] HRMS(ESI-TOF)m / z:[M+Na] + Calcd for C 24 H 16 FNO2SNa + 424.0778; Found424.0781.

[0078] Single crystal data of product 6e are as follows Figure 1 As shown in Table 2:

[0079] Table 2Crystal data and structure refinement for 6e.

[0080]

[0081]

[0082] Example 6

[0083] Product 6f

[0084] (R)-4-benzoyl-3-(4-fluorophenyl)-2,3-dihydro-1 H-benzo[4,5]thiazolo[3,2- a]pyridin-1-one

[0085]

[0086] Yellow solid, 97% yield.

[0087] 1 H NMR (600 MHz, CDC13) δ (ppm): 8.46 (d, J = 7.8 Hz, 1H), 7.61 (dd, J = 7.8, 1.8 Hz, 1H), 7.42 - 7.36 (m, 2H), 7.34 (t, J = 7.2 Hz, 1H), 7.31 - 7.27 (m, 2H), 7.26 - 7.23 (m, 2H), 7.05 (dd, J = 9.0, 4.8 Hz, 2H), 7.00 - 6.95 (m, 2H), 4.33 (dd, J = 7.2, 2.4 Hz, 1H), 3.27 (dd, J = 15.6, 7.2 Hz, 1H), 3.00 (dd, J = 15.6, 2.4 Hz, 1H).

[0088] 13 C NMR (151 MHz, CDC13) δ (ppm): 191.2, 167.6, 162.0 (C-F, 1 J C-F = 245.8 Hz), 156.2, 139.3, 136.5, 136.0, 130.3, 128.4 (C-F, 3 J C-F = 7.2 Hz), 128.1, 127.7, 127.1, 126.8, 126.0, 122.0, 117.5, 116.2 (C-F, 2 J C-F = 21.7 Hz), 107.5, 41.5, 37.9.

[0089] HRMS (ESI-TOF) m / z: [M + Na] Calcd for C + C 24 H 16 FNO2SNa + 424.0778; Found 424.0784.

[0090] Example 7

[0091] Product 6g

[0092] (R)-4-benzoyl-3-(4-methoxyphenyl)-2,3-dihydro-1 H- benzo [4, 5] thiazolo [3, 2-a] pyridin-1 -one

[0093]

[0094] Yellow solid, 82% yield.

[0095] 1 H NMR (600 MHz, CDC13) δ (ppm): 8.46 (d, J = 7.2 Hz, 1H), 7.60 (d, J = 9.0 Hz, 1H), 7.41 - 7.37 (m, 1H), 7.36 (d, J = 7.8 Hz, 1H), 7.33 (t, J = 7.2 Hz, 1H), 7.32 - 7.26 (m, 4H), 7.01 (d, J = 9.0 Hz, 2H), 6.82 (d, J = 9.0 Hz, 2H), 4.29 (dd, J = 7.2, 2.4 Hz, 1H), 3.77 (s, 3H), 3.24 (dd, J = 16.2, 6.6 Hz, 1H), 3.01 (dd, J = 16.2, 2.4 Hz, 1H).

[0096] 13 C NMR (151 MHz, CDC13) δ (ppm): 191.2, 168.0, 158.8, 156.0, 139.3, 136.0, 132.5, 130.2, 128.0, 127.84, 127.77, 126.99, 126.96, 125.8, 121.9, 117.5, 114.6, 108.0, 55.2, 41.6, 37.8.

[0097] HRMS (ESI-TOF) m / z: [M + Na] Calcd for C + Calcd for C 25 H 19 NO3SNa + 436.0978; Found 436.0978.

[0098] Example 8

[0099] Product 6h

[0100] (R)-4-benzoyl-3-(3-bromophenyl)-2,3-dihydro-1 H- benzo [4, 5] thiazolo [3, 2-a] pyridin-1 -one

[0101]

[0102] Yellow solid, 85% yield.

[0103] 1 H NMR (600 MHz, CDC13) δ (ppm): 8.46 (d, J = 9.0 Hz, 1H), 7.61 (d, J = 7.8 Hz, 1H), 7.43 - 7.33 (m, 4H), 7.33 - 7.28 (m, 2H), 7.24 (d, J = 8.4 Hz, 2H), 7.19 (s, 1H), 7.15 (t, J = 7.8 Hz, 1H), 7.02 (d, J = 8.4 Hz, 1H), 4.31 (dd, J = 6.6, 1.8 Hz, 1H), 3.28 (dd, J = 15.6, 6.6 Hz, 1H), 3.03 (dd, J = 16.2, 2.4 Hz, 1H).

[0104] 13 C NMR (151 MHz, CDC13) δ (ppm): 191.2, 167.4, 156.5, 143.3, 139.3, 135.9, 130.9, 130.8, 130.3, 130.1, 128.2, 127.6, 127.1, 126.8, 126.0, 125.2, 123.3, 122.0, 117.6, 106.8, 41.1, 38.3.

[0105] HRMS (ESI-TOF) m / z: [M + Na] Calcd for C + Calcd for C 24 H 16 79 BrNO2SNa + 483.9978, C 24 H 16 81 BrNO2SNa + 485.9957; Found 483.9969, 485.9950.

[0106] Example 9

[0107] Product 6i

[0108] (R)-4-benzoyl-3-(3-methoxyphenyl)-2,3-dihydro-lH-benzo[4,5]thiazolo[3,2- a]pyridin-l-one

[0109]

[0110] Yellow solid, 93% yield.

[0111] 1H NMR (600 MHz, CDC13) δ (ppm): 8.46 (d, J = 8.4 Hz, 1H), 7.60 (d, J = 7.2 Hz, 1H), 7.43 - 7.27 (m, 7H), 7.21 (t, J = 7.8 Hz, 1H), 6.78 (d, J = 7.2 Hz, 1H), 6.70 (d, J = 7.8 Hz, 1H), 6.62 (s, 1H), 4.31 (d, J = 6.6 Hz, 1H), 3.72 (s, 3H), 3.26 (dd, J = 16.2, 6.6 Hz, 1H), 3.04 (d, J = 15.6, 1H).

[0112] 13 C NMR (151 MHz, CDC13) δ (ppm): 191.2, 167.8, 160.2, 156.2, 142.5, 139.4, 136.0, 130.4, 130.2, 128.1, 127.7, 127.03, 127.00, 125.9, 121.9, 118.9, 117.5, 113.0, 112.4, 107.5, 55.1, 41.3, 38.6.

[0113] HRMS (ESI-TOF) m / z: [M + Na] Calcd for C + Calcd for C 25 H 19 NO3SNa + 436.0978; Found 436.0973.

[0114] Example 10

[0115] Product 6j

[0116] (S)-4-benzoyl-3-(2-chlorophenyl)-2,3-dihydro-lH-benzo[4,5]thiazolo[3,2- a]pyridin-l-one

[0117]

[0118] Yellow solid, 92% yield.

[0119] 1H NMR (600 MHz, CDC13) δ (ppm): 8.47 (d, J = 8.4 Hz, 1H), 7.62 (dd, J = 7.8, 1.8 Hz, 1H), 7.42 (d, J = 8.4 Hz, 1H), 7.44 - 7.33 (m, 3H), 7.29 - 7.25 (m, 2H), 7.23 (t, J = 7.8 Hz, 1H), 7.19 - 7.15 (m, 3H), 7.12 (dd, J = 7.8, 2.4 Hz, 1H), 4.74 (dd, J = 7.8, 1.8 Hz, 1H), 3.22 (dd, J = 16.8, 7.8 Hz, 1H), 3.09 (dd, J = 16.2, 2.4 Hz, 1H).

[0120] 13 C NMR (151 MHz, CDC13) δ (ppm): 191.0, 167.7, 156.9, 139.0, 137.5, 135.9, 133.1, 130.6, 130.3, 129.1, 128.2, 127.9, 127.7, 127.1, 126.6, 126.0, 122.0, 117.5, 106.9, 39.0, 35.9.

[0121] HRMS (ESI-TOF) m / z: [M + Na] + Calcd for C 24 H 16 35 ClNO2SNa + 440.0483, C 24 H 16 37 ClNO2SNa + 442.0453; Found 440.0477, 442.0457.

[0122] Example 11

[0123] Product 6k

[0124] (R)-4-benzoyl-3-thiophen-2-yl-2,3-dihydro-lH-benzo[4,5]thiazolo[3,2- a]pyridin-l-one

[0125]

[0126] Yellow solid, 97% yield.

[0127] 1H NMR (600 MHz, CDC13) δ (ppm): 8.48 (d, J = 8.4 Hz, 1H), 7.58 (d, J = 7.8 Hz, 1H), 7.45 - 7.41 (m, 3H), 7.39 - 7.30 (m, 4H), 7.16 (d, J = 6.6 Hz, 1H), 6.89 (dd, J = 5.4, 4.2 Hz, 1H), 6.78 (d, J = 3.6 Hz, 1H), 4.62 (dd, J = 6.0, 3.0 Hz, 1H), 3.27 (dd, J = 16.2, 6.6 Hz, 1H), 3.16 (dd, J = 16.2, 2.4 Hz, 1H).

[0128] Proton-NMR (600 MHz, CHLOROFORM-D) δ 8.47 (d, J = 8.4 Hz, 1H), 7.63 (d, J = 9.0 Hz, 1H), 7.44 (d, J = 8.3 Hz, 1H), 7.39 (t, J = 7.9 Hz, 1H), 7.36 (t, J = 7.6 Hz, 1H), 7.25 (t, J = 6.9 Hz, 1H), 7.16 - 7.21 (m, 3H), 7.11 (d, J = 8.3 Hz, 1H), 6.94 - 6.97 (m, 2H), 4.73 (dd, J = 6.9, 2.1 Hz, 1H), 3.22 (q, J = 7.8 Hz, 1H), 3.10 (dd, J = 15.8, 2.1 Hz, 1H)

[0129] 13 C NMR (151 MHz, CDC13) δ (ppm): 190.6, 167.5, 156.4, 144.8, 139.2, 136.0, 130.4, 128.2, 127.6, 127.3, 127.0, 125.9, 125.0, 124.7, 121.9, 117.6, 108.3, 41.5, 34.3.

[0130] HRMS (ESI-TOF) m / z: [M + H] + Calcd for C 22 H 16 NO2S2 + 390.0617; Found 390.0609.

[0131] Example 12

[0132] Product 6l

[0133] (R)-4-benzoyl-3-naphthalen-1-yl-2,3-dihydro-1H-benzo[4,5]thiazolo[3,2-a]pyridin-1-one (R)-4-benzoyl-3-naphthalen-1-yl-2,3-dihydro-1H-benzo[4,5]thiazolo[3,2-a]pyridin-1-one

[0134]

[0135] Yellow solid, 85% yield.

[0136] 1 H NMR (600 MHz, CDC13) δ (ppm): 8.45-8.41 (m, 1H), 7.93 (d, J = 8.4 Hz, 1H), 7.81 (dd, J = 13.8, 7.8 Hz, 2H), 7.66-7.63 (m, 1H), 7.56-7.49 (m, 2H), 7.39-7.31 (m, 4H), 7.26 (t, J = 6.6 Hz, 1H), 7.21 (d, J = 7.8 Hz, 2H), 7.09-7.04 (m, 2H), 5.16 (dd, J = 7.2, 2.4 Hz, 1H), 3.36 (dd, J = 15.6, 6.6 Hz, 1H), 3.17 (dd, J = 15.6, 1.8 Hz, 1H).

[0137] 13 C NMR (151 MHz, CDC13) δ (ppm): 190.8, 167.7, 156.9, 139.0, 136.0, 135.2, 134.7, 130.3, 129.9, 129.5, 128.6, 128.0, 127.9, 127.0, 126.8, 126.7, 125.9, 125.7, 124.3, 122.1, 122.0, 117.5, 107.6, 40.1, 34.8.

[0138] HRMS (ESI-TOF) m / z: [M + Na] Calcd for C + Calcd for C 28 H 19 NO2SNa + 456.1029; Found 456.1036.

[0139] According to the above test results, the catalyst of the present application has excellent catalytic activity, not only can get catalytic product with excellent yield (up to 99%), but also can realize the enantioselectivity from medium to excellent (up to 95:5er). And according to the research, the compound skeleton synthesized by the catalyst has the activity of resisting hepatitis C virus (HCV), resisting flavivirus and resisting dengue virus.

[0140] The preparation of the chiral phase transfer catalyst of the present application has strong operability, high yield, and good catalytic activity, and obtains catalytic product with optical activity, and has wide market application prospect.

[0141] The above merely describes the preferred embodiments of the present application and is not used to limit the present application. Based on the above description of the present application, those skilled in the art can make modifications, replacements or changes in other forms without departing from the above basic technical ideas of the present application, according to the common technical knowledge and experience in the art. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principle of the present application shall be included in the protection scope of the present application.

Claims

1. A chiral phase transfer catalyst characterized in that, The structure of the chiral phase transfer catalyst is:

2. A process for the preparation of the chiral phase transfer catalyst of claim 1, characterized in that, The method comprises: sequentially adding 1 eq of octenidine 1, toluene and 1.3-1.5 eq of 4-methyl formate benzyl bromide 2 into a sealed tube, refluxing the reaction solution for 3-5 hours, filtering after cooling after the reaction is completed, washing and drying the solid with toluene, and obtaining the target product 3, which is the bromide salt of (1S,2S,4S,5R)-2((S)-hydroxyquinoline-4-methyl)-1-(4-methoxycarbonyl)benzyl)-5-vinyl quinuclidine-1-on, the reaction formula is as follows:

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