Dendritic chiral phase-transfer catalysts and their use in the catalysis of asymmetric alkylations of amino acid derivatives

Abstract

The application belongs to the technical field of chiral catalysis and medicine, and particularly relates to a dendritic chiral phase transfer catalyst, a structural formula of which is shown as formula (I) or formula (II). A series of chiral phase transfer catalysts based on soluble dendritic macromolecules are synthesized by changing the number of repeated carbon chains on the core molecular structure, and it is found through catalyzing asymmetric alkylation of amino acid derivatives that the dendritic chiral phase transfer catalysts provided by the application have excellent yield and enantioselectivity in catalyzing preparation of chiral amino acid derivatives.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of chiral catalysis and medicine, and particularly relates to a dendritic chiral phase transfer catalyst and its application in asymmetric alkylation of amino acid derivatives. BACKGROUND

[0002] Over the past decade, successful therapeutic targets and improved drug delivery methods have been developed for various diseases such as diabetes, cancer, osteoporosis, multiple sclerosis, HIV infection and chronic pain. Therefore, the development of polypeptide drugs in the world pharmaceutical market is changing rapidly. In addition, there are more than 80 candidate peptide drugs in the clinic, and a large number of preclinical research projects are currently being carried out all over the world. At present, there is an increasing demand for efficient synthesis of various types of unnatural amino acids in a high-purity and low-cost manner. The asymmetric phase transfer catalyst used in the asymmetric alkylation reaction of amino acid Schiff base creates a unique advantage in economy and quality in the process development of large-scale synthesis of unnatural amino acids. However, there are few reported examples of dendrimer-based chiral phase transfer catalysts. SUMMARY

[0003] The primary object of the present application is to fill the gap in this field in view of the fact that there are few reported examples of dendrimer-based chiral phase transfer catalysts. The present application first provides the design and synthesis of a series of dendrimer-based chiral phase transfer catalysts based on a simplified Maruoka catalyst, as well as their application in the asymmetric synthesis of natural and unnatural amino acid derivatives.

[0004] The present application synthesizes a series of dendrimer-based chiral phase transfer catalysts by changing the number of repeating carbon chains on the core molecular structure, and evaluates them through asymmetric alkylation of amino acid Schiff base. Excellent yield and enantioselectivity are observed using a dendritic chiral phase transfer catalyst with 8 carbon units. Theoretical studies on the most effective dendrimer-based chiral phase transfer catalyst show that the chiral ammonium center has a favorable special arrangement in the catalyst.

[0005] To achieve the above object, the technical scheme adopted by the present application is:

[0006] A dendritic chiral phase transfer catalyst, the structural formula of which is shown in formula (i) or formula (ii):

[0007]

[0008] wherein Ar is 3,4,5-F3-C6H2 or (3,5-CF3-C6H3), and n is any natural number from 1 to 20.

[0009] As a more preferred technical solution, n in formula (i) is 2, 4, 6, 8, 10 or 12.

[0010] As a preferred technical solution, n in formula (ii) is 2 or 4.

[0011] The present application also protects the use of the dendritic chiral phase transfer catalyst in catalyzing asymmetric alkylation of amino acid derivatives.

[0012] Compared with the prior art, the present application has the following beneficial effects:

[0013] The present application synthesizes a series of chiral phase transfer catalysts based on soluble dendritic macromolecules by changing the number of repeating carbon chains on the core molecular structure, and finds that the dendritic chiral phase transfer catalyst has excellent yield and enantioselectivity through asymmetric alkylation catalysis of amino acid Schiff bases. BRIEF DESCRIPTION OF DRAWINGS

[0014] Figure 1 Figure 4 is a catalytic product effect diagram of PTC-5 for asymmetric benzylation reaction.

[0015] Figure 2 TAB A is used as a control product to test the reaction product, and the S-type and R-type products obtained are 1:1. DETAILED DESCRIPTION

[0016] The technical solutions of the present application will be described clearly and completely below in combination with the embodiments of the present application. Obviously, the described embodiments are only some of the embodiments of the present application, but not all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor fall within the scope of protection of the present application.

[0017] The test methods used in the embodiments of the present application are conventional methods unless otherwise specified; the materials, reagents, etc. used are commercially available reagents and materials unless otherwise specified.

[0018] I. Synthesis method:

[0019] (1) PTC-1 to -6 are synthesized as shown below:

[0020]

[0021] (a) Br(CH2) nBr (9 eq.), potassium carbonate (4.3 eq.), N,N-dimethylformamide, room temperature, 24 h; (b) N-methylbenzylamine (6 eq.), potassium carbonate (6 eq.), acetonitrile, reflux, 8 h; (c) palladium on carbon, hydrogen, methanol / acetic acid, room temperature, 5 h; (d) potassium carbonate (3 eq.), acetonitrile, reflux, 10 h.

[0022] According to the reported method, the monoalkylation of 3,5-dimethoxyphenol with α,ω-dibromoalkanes in the presence of potassium carbonate in acetonitrile at reflux for 10 h gave 1g and 1h in 70% and 76% yield, respectively. Then, the benzylamination of 1g and 1h with N-methylbenzylamine in the presence of potassium carbonate in acetonitrile at reflux for 8 h gave 2g and 2h in 69% and 95% yield, respectively. Subsequently, the deprotection of the benzyl groups of 2g and 2h with 5% palladium on carbon in the presence of hydrogen in methanol / acetic acid (2:1, v / v) at room temperature for 8 h gave 3g and 3h in 67-70% yield. Finally, the reaction of 3g and 3h with (S)-3,3'-bis(3,4,5-trifluorophenyl)-2,2'-bis(bromomethyl)-1,1'-binaphthyl (4) in the presence of potassium carbonate in acetonitrile at reflux for 12 h gave PTC-7 and -8 in 47-53% yield, respectively.

[0023] (2) Synthesis of PTC-7 and -8 as shown below:

[0024]

[0025] According to the reported method, the monoalkylation of 3,5-dimethoxyphenol with α,ω-dibromoalkanes in the presence of potassium carbonate in acetonitrile at reflux for 10 h gave 1g and 1h in 70% and 76% yield, respectively. Then, the benzylamination of 1g and 1h with N-methylbenzylamine in the presence of potassium carbonate in acetonitrile at reflux for 8 h gave 2g and 2h in 69% and 95% yield, respectively. Subsequently, the deprotection of the benzyl groups of 2g and 2h with 5% palladium on carbon in the presence of hydrogen in methanol / acetic acid (2:1, v / v) at room temperature for 8 h gave 3g and 3h in 67-70% yield. Finally, the reaction of 3g and 3h with (S)-3,3'-bis(3,4,5-trifluorophenyl)-2,2'-bis(bromomethyl)-1,1'-binaphthyl (4) in the presence of potassium carbonate in acetonitrile at reflux for 12 h gave PTC-7 and -8 in 47-53% yield, respectively.

[0026] wherein, in the reaction formula (a) Br(CH2) nBr (8 eq), potassium carbonate (8 eq), acetonitrile, reflux, 10 h; (b) N-methylbenzylamine (2 equiv), potassium carbonate (2 equiv), acetonitrile, reflux, 8 h; (c) palladium on carbon, hydrogen, methanol / acetic acid, room temperature, 12 h; (d) potassium carbonate (1.1 eq), acetonitrile, reflux, 12 h.

[0027] (3) Compound characterization data:

[0028] [1a]

[0029]

[0030] (100 MHz, CDC13): δ 160.2, 95.2, 68.1, 29.1.

[0031] [1b]

[0032]

[0033] 28.0, 25.4.

[0034] [1c]

[0035]

[0036] 28.0, 25.4.

[0037] [1d]

[0038]

[0039] δ 161.1, 94.0, 68.1, 34.1, 32.9, 29.3, 29.3, 28.8, 28.2, 26.1.

[0040] [1e]

[0041]

[0042] 29.4, 29.3, 29.2, 28.8, 28.2, 26.1.

[0043] [1f]

[0044]

[0045] CDCl3)δ161.0,93.8,68.0,34.1,32.8,29.54,29.52,29.5,29.44,29.4,29.3,28.8,28.2,26.1; IR(KBr):2920,2850,1728,1590,1466,1445,1391,1262,1210,1158,1078,1058,835,724,650cm -1 .HRMS(ESI):calcd for[M+H] + 869.3298 found 869.3292.

[0046] 1-(2-Bromoethoxy)-3,5-dimethoxybenzene[1g]

[0047]

[0048] (t,J=8.2Hz,2H),3.70(s,6H),3.56(t,J=6.2Hz,2H); 13 C NMR (75MHz, CDCl3): δ161.6,159.9,93.6,67.8,55.4,29.1.

[0049] 1-(4-Bromobutoxy)-3,5-dimethoxybenzene[1h]

[0050]

[0051] 3.95(t,J=6.0Hz,2H),3.78(s,6H),3.50-3.46(m,2H),2.08-2.04(m,2H),1.96-1.89(m,2H); 13 C NMR (100MHz, CDCl3): δ161.5,160.8,93.4,93.0,66.9,55.4,33.5,29.5,27.9; IR(KBr)2924,2842,1597,1463,1392,1204,1151,1063,818,682cm -1 .HRMS(ESI):[M+H] + calcd for C 12 H 18 BrO3 + 289.0434,found 289.0433.

[0052] [2a]

[0053]

[0054] 139.9, 129.0, 128.3, 127.0, 94.0, 66.7, 59.4, 54.4, 52.6, 29.5, 20.6, 14.2; IR (KBr): 2954, 1703, 1600, 1494, 1455, 1372, 1250, 1162, 1028, 909, 820, 734, 698, 680, 621, 467 cm -1 HRMS (ESI): [M+H] + calcd for C 45 H 64 N3O3 + 694.4942, found 694.4938.

[0055] [2b]

[0056]

[0057] MHz, CDCl3): δ 161.0, 140.3, 129.0, 128.2, 126.8, 94.0, 67.9, 58.8, 53.7, 53.4, 29.4, 27.2, 23.7, 20.7, 14.2; IR (KBr): 2952, 2796, 1600, 1494, 1455, 1384, 1301, 1247, 1206, 1162, 1065, 1028, 966, 912, 816, 733, 698, 680, 620, 471 cm -1 HRMS (ESI): [M+H] + calcd for C 51 H 76 N3O3 + 778.5881, found 778.5877.

[0058] [2c]

[0059]

[0060] 58.7, 53.7, 53.6, 29.4, 29.2, 27.3, 27.0, 26.1, 20.7, 14.2; IR (KBr): 2932, 2859, 2795, 1600, 1494, 1463, 1385, 1163, 1067, 1028, 815, 732, 698 cm -1 HRMS (ESI): [M+3H] 3+ calcd for C 57 H 90 N3O3 3+288.2322, found 288.2321.

[0061] [2d]

[0062]

[0063] 0.87 (t, J = 7.4 Hz, 9H,) ; 13 C NMR (100 MHz, CDC13): δ 161.1, 140.2, 128.9, 128.1, 126.7, 93.9, 68.0, 58.6, 53.8, 53.6, 29.5, 29.4, 29.3, 29.2, 27.4, 27.0, 26.1, 20.6, 14.1; IR (KBr): 2929, 2857, 2795, 1600, 1494, 1463, 1384, 1301, 1249, 1162, 1062, 1066, 1028, 815, 733, 698 cm -1 HRMS (ESI): [M + H] + calcd for C 63 H 100 N3O3 + 946.7759, found 946.7752.

[0064] [2e]

[0065]

[0066] 127.7, 93.7, 67.9, 57.8, 53.0, 52.7, 29.4 (2C), 29.3 (2C), 29.2, 27.6, 27.1, 26.0, 25.5, 20.4, 13.9; IR (KBr): 2927, 2854, 2795, 1600, 1494, 1463, 1385, 1162, 1066, 1028, 816, 732, 699 cm -1 HRMS (ESI): [M + 3H] 3+ calcd for C 69 H 114 N3O3 3+ 344.2948, found 344.2947.

[0067] [2f]

[0068]

[0069] 138.6, 129.3, 128.4, 127.2, 93.8, 68.1, 58.4, 53.6, 53.3, 34.2, 32.9, 29.7, 29.6, 29.5, 29.4, 29.3, 28.9, 28.3, 27.5, 26.2, 20.7, 14.1; IR: (KBr) 2913, 2846, 2787, 1601, 1473, 1444, 1359, 1138, 1043, 1012, 735, 786 cm -1 HRMS (ESI): [M + 3H] 3+ calcd for C 75 H 126 N3O3 3+ 372.3261, found 372.3253.

[0070] [2g]

[0071]

[0072] 2.33 (s, 3H); 1.78-1.72 (m, 2H), 1.66-1.59 (m, 2H); 13 C NMR (100 MHz, CDC13): δ 161.5, 160.8, 138.8, 129.1, 128.3, 127.1, 93.4, 93.1, 66.3, 62.7, 55.8, 55.4, 42.9; IR (KBr): 2927, 2840, 1601, 1456, 1204, 1152, 1065, 818, 739, 699 cm -1 HRMS (ESI): [M + H] + calcd for C 18 H 24 NO3 + 302.1751, found 302.1751

[0073] [2h]

[0074]

[0075] 2.33 (s, 3H); 1.78-1.72 (m, 2H), 1.66-1.59 (m, 2H); 13C NMR (100 MHz, CDC13): δ 161.5, 161.0, 138.6, 129.2, 128.3, 127.1, 93.4, 92.9, 67.8, 62.2, 56.8, 55.3, 42.0, 27.0, 23.7; IR (KBr): 2927, 2840, 2788, 1601, 1471, 1205, 1194, 1153, 1066, 820, 740, 699, 681 cm -1 HRMS (ESI): [M + H] + calcd for C 20 H 28 NO3 + 330.2064, found 330.2064

[0076] [3a]

[0077]

[0078] 9H); 13 C NMR (100 MHz, CDC13): δ 160.8, 94.4, 67.4, 49.7, 48.9, 32.3, 20.6, 14.1; IR (KBr): 2956, 2871, 1593, 1456, 1377, 1244, 1212, 1166, 1065, 816, 734, 679 cm -1 HRMS (ESI): [M + H] + calcd for C 24 H 46 N3O3 + 424.3534, found 424.3529.

[0079] [3b]

[0080]

[0081] 1.36-1.29 (m, 6H), 0.89 (t, J = 7.2 Hz, 9H); 13 C NMR (100 MHz, CDC13): δ 160.8, 93.9, 67.8, 49.7, 49.6, 32.2, 27.1, 26.7, 20.5, 14.0; IR (KBr): 2926, 2856, 1599, 1463, 1380, 1163, 1064, 815 cm -1 HRMS (ESI): [M + H] + calcd for C 30 H 58N3O3 + 508.4473, found 508.4471.

[0082] [3c]

[0083]

[0084] MHz, CDCl3): δ 160.9, 93.8, 67.9, 50.0, 49.8, 32.3, 30.1, 29.2, 27.2, 26.0, 20.5, 14.0. IR (KBr): 2928, 2856, 1597, 1464, 1388, 1165, 1063, 806 cm -1 HRMS (ESI): [M+H] + calcd for C 36 H 70 N3O3 + 592.5412, found 592.5408.

[0085] [3d]

[0086]

[0087] 161.1, 93.9, 68.1, 50.3, 50.0, 32.5, 30.3, 29.6, 29.4, 29.3, 27.5, 26.1, 20.7, 14.2; IR (KBr): 2931, 2855, 2799, 1596, 1461, 1165, 1060, 815, 725 cm -1 HRMS (ESI): [M+H] + calcd for C 42 H 82 N3O3 + 676.6351, found 676.6346.

[0088] [3e]

[0089]

[0090] MHz, CDCl3): δ 160.9, 93.7, 68.0, 50.2, 49.9, 32.4, 30.2, 29.7, 29.6, 29.5, 29.4, 29.2, 27.5, 26.1, 20.5, 14.1; IR (KBr): 2926, 2854, 1600, 1463, 1385, 1162, 1063, 815, 722, 680 cm -1 HRMS (ESI): [M+H] +C 48 H 94 N3O3 + 760.7289, found 760.7285.

[0091] [3f]

[0092]

[0093] MHz, CDCl3): δ 161.0, 93.8, 68.0, 50.2, 49.8, 32.3, 30.2, 29.6 (5C), 29.4, 29.3, 27.4, 26.1, 20.6, 14.0; IR (KBr): 925, 2852, 1592, 1411, 1266, 1163, 1058, 722, 656, 618 cm -1 HRMS (ESI): [M + 3H] 3+ calcd for C 54 H 108 N3O3 3+ 282.2791, found 282.2790.

[0094] [3g]

[0095]

[0096] δ 161.5, 160.7, 93.4, 93.1, 66.8, 55.3, 50.6, 36.1; IR (KBr): 2924, 2851, 1599, 1456, 1376, 1205, 1152, 1066, 819, 738, 699, 681 cm -1 HRMS (ESI): [M + H] + calcd for C 11 H 18 NO 3+ 212.1281, found 212.1278.

[0097] [3h]

[0098]

[0099] 2H); 13C NMR (100 MHz, CDC13): δ 161.5, 160.9, 93.4, 92.9, 67.7, 55.3, 51.5, 36.1, 27.0, 26.2; IR (KBr): 2925, 2854, 1602, 1463, 1386, 1205, 1152, 1066, 818, 734, 684 cm - 1 HRMS (ESI): [M + H] + calcd for C 13 H 22 NO3 + 240.1594, found 240.1594.

[0100] PTC-1

[0101]

[0102] 0.90-0.88 (m, 3H), 0.67 (t, J = 7.2 Hz, 9H), 0.54-0.52 (m, 3H); 13 C NMR (100 MHz, CDC13): δ 161.5, 160.9, 93.4, 92.9, 67.7, 55.3, 51.5, 36.1, 27.0, 26.2; IR (KBr): 2925, 2854, 1602, 1463, 1386, 1205, 1152, 1066, 818, 734, 684 cm C-F = 240.0 Hz), 139.9, 139.8, 137.2-136.7 (m), 135.4-135.3 (m), 133.1, 132.9, 132.5, 132.4, 130.1, 129.6, 129.0, 128.6, 124.7-124.6 (m), 116.3-116.1 (m), 95.9, 63.2, 60.1, 59.7, 59.2, 56.4, 25.9, 20.4, 13.8; IR (KBr) 3417, 2926, 1724, 1615, 1448, 1424, 1362, 1242, 1210, 1156, 1047, 894, 859, 801, 781, 752, 727, 710, 679 cm - 1 HRMS (ESI): [M - 3Br] 3+ calcd for C 126 H 96 F 18 N3O3 3+ 680.5727, found 680.5726.

[0103] PTC-2

[0104]

[0105] 1.03-0.74(m,12H),0.42-0.39(m,12H),0.16-0.16(m,3H); 13 C NMR(100 MHz,CDCl3):δ160.3,151.2(d,J C-F =246.4 Hz),141.2-141.0(m),138.6,138.5,137.2,135.0-134.9(m),133.7,131.5,131.4,131.1,128.6,127.9,127.6,123.7,115.3-114.3(m),95.6,66.4,57.6,57.5,57.1,29.8,25.3,24.4,19.3,13.0;IR(KBr):3385,2962,2928,2857,1161,1525,1469,1447,1423,1360,1260,1242,1156,1095,1045,893,859,803,750,727,707,678 cm -1 .HRMS(ESI):[M-3Br] 3+ calcd for C 132 H 108 F 18 N3O3 3+ 708.6040 found708.6034.

[0106] PTC-3

[0107]

[0108] J=7.0 Hz,9H),0.28-0.22(m,6H); 13 C NMR(100 MHz,CD3OD)δ160.9,151.2(d,J C-F =268.1 Hz),138.4,137.1,135.9-135.7(m),133.9,131.5,131.1,128.7,128.2,127.6,127.2,123.5,115.2-114.7(m),93.5,67.3,56.8,56.7,56.6,28.8,25.7,25.2,24.3,22.5,18.9,12.3;IR(KBr):3404,2961,1615,1527,1470,1448,1362,1243,1159,1047,894,862,803,752 cm -1 .HRMS(ESI):[M-3Br] 3+calcd for C 138 H 120 F 18 N3O3 3+ 736.6353,found736.6353.

[0109] PTC-4

[0110]

[0111] 1.30-0.91(m,30H),0.74(t,J=7.0 Hz,9H),0.38-0.26(m,6H); 13 C NMR(100 MHz,CD3OD)δ162.4,152.3(d,J C-F =243.8 Hz),139.8-139.7(m),138.5-138.4(m),137.3-137.1(m),135.3,132.9-132.8(m),132.5,130.1,129.6,129.0,128.6,124.8,116.6-115.9(m),94.9,68.9,58.2,58.0,57.9,30.8,30.5,30.3(2C),27.1,27.0,25.6,23.8,20.3,13.7 cm -1 ;IR(KBr)3378,2927,1614,1526,1498,1470,1447,1424,1361,1258,1242,1212,1158,1046,894,859,846,751,728 cm -1 .HRMS(ESI):[M-3Br] 3+ calcd for C 144 H 132 F 18 N3O3 3+ 764.6666,found 764.6663.

[0112] PTC-5

[0113]

[0114] 6H),1.39-0.87(m,42H),0.79(t,J=7.0 Hz,9H),0.43-0.25(m,6H); 13 C NMR(100MHz,CD3OD):δ161.0,151.2(d,J C-F=242.7 Hz),141.1-140.8(m),138.4,138.3,137.1,135.8-135.7(m),133.9,131.6,131.5,131.1,128.7,128.2,127.6,127.2,123.5,115.3-114.5(m),93.6,67.6,56.9,56.7,56.6,29.2,29.1,29.05,29.0,28.9,25.8,25.7,24.3,22.5,18.9,12.4;IR(KBr):3386,2929,2856,1614,1526,1470,1448,1424,1362,1243,1158,1047,894,753,727cm -1 .HRMS(ESI):[M-3Br] 3+ calcd for C 150 H 144 F 18 N3O3 3+ 792.6979,found 792.6979.

[0115] PTC-6

[0116]

[0117] 60H),0.79(t,J=7.0 Hz,9H),0.43-0.25(m,6H); 13 C NMR(100 MHz,CD3OD):δ161.0,151.7(d,J C-F =257.4 Hz),138.4,138.3,137.1,135.8,133.9,131.6,131.5,131.1,129.7,128.7,128.3,127.7,127.2,123.4,115.2-114.5(m),93.6,67.6,56.8,56.7,56.5,30.8,29.3,29.2,29.1,29.1,29.0,29.0,28.7,25.7,24.3,22.5,18.9,12.4.IR(KBr):3386,2929,2856,1614,1526,1470,1448,1424,1362,1243,1158,1047,894,753,727 cm - 1 .HRMS(ESI):[M-3Br] 3+ calcd forC 156 H 156F 18 N3O3 3+ 820.7292,found 820.7301.

[0118] PTC-7

[0119]

[0120] J=13.6Hz,1H),5.01(d,J=13.6Hz,1H),4.01-3.99(m,3H),3.93(d,J=13.6Hz,1H),3.76(d,J=14.0Hz,1H),3.68(s,6H),3.53-3.46(m,1H),2.98(s,3H). 13 C NMR(100MHz,CDCl3):δ161.6,158.4,151.3(d,J C-F =249.9Hz),138.4,138.3,137.3,137.2,134.5-134.4(m),133.8,133.7,131.7,131.4,131.0,128.8,128.2,128.1,127.4,123.9,123.2,115.0-114.5(m),94.9,92.9,62.1,61.2,60.8,59.1,55.5,47.3.IR(KBr):2922,2848,2539,2341,1615,1595,1527,1472,1448,1362,1205,1153,1066,1046,897,727cm -1 .HRMS(ESI):[M-Br] + calcd for C 45 H 34 F6NO3 + 750.2437,found 750.2442.

[0121] PTC-8

[0122]

[0123] 4H),5.96-5.95(m,1H),5.88-5.87(m,2H),4.92(d,J=13.8Hz,1H),4.83(d,J=13.2Hz,1H),3.75-3.60(m,11H),2.85-2.80(m,1H),2.77(s,3H),1.55-1.35(m,4H). 13C NMR (75 MHz, CDC13): δ 161.3, 160.5, 151.3 (d, J C-F = 246.0 Hz), 141.6, 138.3, 138.0, 137.3, 136.9, 134.7-133.7 (m), 131.4, 131.0, 130.9, 128.7, 128.0, 127.4, 123.8, 123.4, 114.9-114.6 (m), 93.4, 93.2, 66.7, 61.1, 57.8, 55.3, 47.0, 29.7, 25.7, 20.0. HRMS (ESI): [M-Br] + calcd for C 47 H 38 F6NO3 + 778.2750, found 778.2755.

[0124] II. Catalytic Test:

[0125] N-Benzylidene glycine tert-butyl ester and 1 mol% of dendritic chiral phase transfer catalyst PTC-1 in toluene 50% aqueous potassium hydroxide solution under the conditions of asymmetric benzylation reaction for 9 hours to obtain glycine tert-butyl ester derivative 6 with 93% yield and 89% ee (enantiomeric excess), as shown in Table 1, and the reaction formula is as follows:

[0126]

[0127] Table 1 Evaluation of dendritic chiral phase transfer catalysts PTC-1-8 in asymmetric benzylation reaction of glycine Schiff base 5

[0128]

[0129] As shown in Table 1, in sharp contrast, under similar asymmetric phase transfer conditions, the corresponding monomethylammonium salt PTC-7 obtained product 6 with 68% yield and 69% ee, which indicates the synthesis advantage of dendritic PTC-1 in chiral amino acid synthesis. When dendritic PTC-2 with tetramethylene dendritic structure is applied to the asymmetric benzylation reaction of glycine Schiff base 5, compared with dendritic catalyst PTC-1 with dimethyl dendritic structure, similar reactivity and enantioselectivity are observed. In addition, under similar asymmetric phase transfer conditions, using monomethylammonium salt PTC-8, compared with PTC-7, product 6 is obtained with higher yield and slightly better enantioselectivity.

[0130] Further investigation of dendrimer-based chiral phase transfer catalysts PTC-3 to -6 revealed that while the dendrimer catalyst PTC-3, with a hexamethylene branch structure, produced the glycine tert-butyl ester derivative 6 in 95% yield with an ee of 87%, the dendrimer catalysts PTC-4 and PTC-5, with octamethylene and decamethylene branches, exhibited significantly better enantioselectivities, with ee values ​​of 94% and 93%, respectively. Notably, extending the branch structure to octamethylene and decamethylene units (PTC-4 and PTC-5, respectively) resulted in asymmetric benzylation reactions with high yields (96% and 93%, respectively) and excellent enantioselectivities (94% and 93% ee, respectively). Further extending the branch structure to dodecamethylene units (PTC-6), however, resulted in decreased yields (91%) and enantioselectivities (90% ee). Thus, the structure-activity relationship between the ammonium cation part of the simplified Maruoka catalyst and the dendrimer-based phloroglucinol part in asymmetric phase transfer catalysis was experimentally elucidated.

[0131] Obviously, the specific implementation scheme described above is only a further detailed description of the purpose, technical solutions and beneficial effects of the present invention. It should be understood that the above is only a specific example of the present invention and is not intended to limit the present invention. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. A dendritic chiral phase transfer catalyst, characterized in that The structural formula is shown in formula (i): ； Wherein, Ar is 3,4,5-F3-C6H2- or 3,5-(CF3)2-C6H3-, and n is any natural number from 1 to 20.

2. Use of the dendritic chiral phase transfer catalyst according to claim 1 in the catalysis of asymmetric alkylation of amino acid derivatives.

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