A process for the preparation of 3,4-dihydropyrane derivatives

Abstract

The application discloses a preparation method of 3,4-dihydropyran derivatives, and a reaction formula is as follows: the unactivated propenal and the weak polar olefin which are simple in structure and low in material cost are used as starting materials, the unactivated propenal and the weak polar olefin which are weak in reactivity can participate in [4+2] cycloaddition, and the 3,4-dihydropyran derivatives with high purity can be prepared; the preparation process is simple in operation, high in yield and excellent in diastereoselectivity, can effectively convert low-cost raw materials into high-value-added compounds, and provides an economic and efficient synthesis strategy for related industries.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of organic synthesis, and particularly relates to a preparation method of 3,4-dihydropyrane derivatives. BACKGROUND

[0002] Many natural products and drug molecules with physiological activity contain 3,4-dihydropyrane or tetrahydropyrane structural units, which play an important role in organic synthesis. The oxaz[4+2] cycloaddition reaction of propenal with olefin is considered to be one of the most direct and efficient methods for preparing 3,4-dihydropyrane structural units. However, due to the weak reactivity between unactivated propenal and weakly polarized olefin, this reaction has certain limitations in practical application. In addition, unactivated propenal is prone to polymerization under the catalysis of strong Lewis acid, which further increases the difficulty of the oxaz[4+2] cycloaddition reaction between unactivated propenal and weakly polarized olefin, making it difficult to achieve this process. SUMMARY

[0003] The present application aims to overcome the defects of the prior art and provide a preparation method of 3,4-dihydropyrane derivatives.

[0004] The technical solution of the present application is as follows:

[0005] A preparation method of 3,4-dihydropyrane derivatives, characterized in that the reaction formula is as follows:

[0006]

[0007] wherein,

[0008] R1 is selected from C1-C5 alkyl, C1-C5 haloalkyl, cycloalkyl and aryl, R2 is selected from H, C1-C3 alkyl,

[0009] R3 is selected from C1-C7 alkyl and C6-C 10 substituted phenyl, R4 is selected from H, C1-C7 alkyl and aryl, R5 is selected from H and C1-C3 alkyl, or R4, R5 and the main body of the obtained 3,4-dihydropyrane derivative form a fused ring structure.

[0010] In a preferred embodiment of the present application, the structural formula of the aryl boron halide is: wherein R is halogen, and Ar is aryl.

[0011] Further preferably, the aryl group is selected from phenyl, 1-naphthyl or substituted phenyl with an electron-withdrawing group.

[0012] In a preferred embodiment of the present application, the solvent is selected from dichloromethane, acetonitrile and 1,2-dichloroethane.

[0013] In a preferred embodiment of the present application, the aryl boron halide has the following structural formula: wherein R is halogen, Ar is aryl, aryl is selected from phenyl, 1-naphthyl or substituted phenyl with electron withdrawing group; and the solvent is selected from dichloromethane, acetonitrile and 1,2-dichloroethane.

[0014] In a preferred embodiment of the present application, the method comprises the following steps:

[0015] (1) mixing the solvent, the aryl boron halide, the unactivated propenal and the weakly polar olefin, and then reacting at -20℃ to room temperature for 40 min to 4 d;

[0016] (2) adding triethylamine to the mixture obtained in step (1) to quench the reaction, to obtain a reaction mixture;

[0017] (3) allowing the reaction mixture obtained in step (2) to stand to room temperature, removing low-boiling substances under reduced pressure, and then purifying by column chromatography to obtain the purified 3,4-dihydropyrane derivative.

[0018] Further preferably, the molar ratio of the triethylamine to the aryl boron halide is 2-3:1.

[0019] In a preferred embodiment of the present application, the molar ratio of the unactivated propenal, the weakly polar olefin and the aryl boron halide is 1.0:1.0-3.0:0.05-0.4.

[0020] Further preferably, the ratio of the unactivated propenal to the solvent is 1 mol:1-3 L.

[0021] The present application has the following advantages:

[0022] 1. The present application uses unactivated propenal and weakly polar olefin as starting materials, which are simple in structure and low in cost, so that the unactivated propenal and the weakly polar olefin with weak reactivity can participate in [4+2] cycloaddition to produce 3,4-dihydropyrane derivatives with high purity. This preparation process is simple in operation, high in yield and excellent in diastereoselectivity, and can effectively convert low-cost raw materials into high-value-added compounds, thereby providing an economic and efficient synthesis strategy for related industries.

[0023] 2. The 3,4-dihydropyrane derivatives synthesized by the present application exhibit potential physiological activity due to their structural characteristics, which makes them have important application prospects in the fields of medicinal chemistry and biological activity research. DETAILED DESCRIPTION

[0024] The technical solutions of the present application are further described and explained in detail through specific embodiments.

[0025] Example 1

[0026] Unactivated propenal is α-ethylpropenal, weakly polar olefin α-methylstyrene, R1 is ethyl, R2 is H, R3 is phenyl, R4 is methyl, and R5 is H.

[0027] Aryl boron halide is Ar is phenyl, and R is chloro.

[0028] The preparation method comprises the following steps:

[0029] (1) 1 mL of dichloromethane, 0.054 mmol of phenyl boron dichloride, 0.27 mmol of α-ethylpropenal and 0.405 mmol of α-methylstyrene are put into a reaction container, and the reaction is carried out at -20 °C overnight;

[0030] (2) 0.11 mmol of triethylamine is added to the reaction system to quench the reaction, and a reaction mixture is obtained;

[0031] (3) The reaction mixture is left to room temperature, low-boiling substances are removed by distillation under reduced pressure, and then purified by column chromatography to obtain a purified 3,4-dihydropyrane derivative.

[0032] The structure of the prepared 3,4-dihydropyrane derivative is The mass is 43.7 mg, and the yield is 80%. The characterization data of the 3,4-dihydropyrane derivative are as follows:

[0033] TLC: R f 0.7 (ethyl acetate / hexane = 1:20) [KMnO4, UV];

[0034] 1 H NMR (500 MHz, CDCl3) 7.38-7.36 (m, 2H), 7.33-7.30 (m, 2H), 7.24-7.20 (m, 1H), 6.30 (s, 1H), 2.20-2.14 (m, 1H), 1.94-1.82 (m, 4H), 1.69-1.61 (m, 1H), 1.49 (s, 3H), 0.90 (t, J = 7.5 Hz, 3H);

[0035] 13 C NMR (126 MHz, CDCl3) δ 146.27, 136.66, 128.22, 126.62, 124.88, 113.82, 76.84, 33.37, 29.09, 26.03, 21.47, 13.06;

[0036] IR (neat) 3037, 2963, 2949, 1671, 1447, 1268, 1192, 1146, 732, 703 cm -1 ;

[0037] HRMS (ESI) exact mass calcd. for C 14 H 18 O: m / z 203.1430 ([M+H] + ), found: m / z 203.1430 ([M+H] + ).

[0038] Example 2

[0039] Unactivated propenal is α-methylpropenal, weakly polar olefin α-methylstyrene, R1 is methyl, R2 is H, R3 is phenyl, R4 is methyl, and R5 is H.

[0040] Aryl boron halide is Ar is phenyl, and R is chloro.

[0041] The preparation method comprises the following steps:

[0042] (1) 1 mL of dichloromethane, 0.054 mmol of phenyl boron dichloride, 0.27 mmol of α-methylpropenal and 0.405 mmol of α-methylstyrene are put into a reaction container, and the reaction is carried out at -20 °C overnight;

[0043] (2) 0.11 mmol of triethylamine is added to the reaction system to quench the reaction, and a reaction mixture is obtained;

[0044] (3) The reaction mixture is left to room temperature, low-boiling substances are removed by distillation under reduced pressure, and then the purified 3,4-dihydropyrane derivative is obtained by column chromatography purification.

[0045] The 3,4-dihydropyrane derivative prepared in the example has the structural formula The mass is 38.6 mg, and the yield is 76%. The characterization data of the 3,4-dihydropyrane derivative are as follows:

[0046] TLC: R f 0.7 (ethyl acetate / hexane = 1:20) [KMnO4, UV];

[0047] 1H NMR (500 MHz, CDCI3) δ 7.37 - 7.35 (m, 2H), 7.32 - 7.29 (m, 2H), 7.23 - 7.20 (m, 1H), 6.27 (s, 1H), 2.20 - 2.15 (m, 1H), 1.94 - 1.88 (m, 1H), 1.83 - 1.78 (m, 1H), 1.69 - 1.61 (m, 1H), 1.48 - 1.47 (m, 6H);

[0048] 13 C NMR (126 MHz, CDCI3) δ 146.22, 137.08, 128.24, 126.62, 124.86, 108.00, 76.58, 33.15, 29.32, 23.66, 18.40;

[0049] IR (neat) 3065, 2979, 2922, 1679, 1493, 1448, 1167, 1140, 761, 695 cm -1 ;

[0050] HRMS (ESI) exact mass calcd. for C 13 H 16 O: m / z 211.1093 ([M+Na] + ), found: m / z 211.1089 ([M+Na] + ).

[0051] Example 3

[0052] Unactivated propenal is α-butyl propenal, weakly polar olefin is α-methyl styrene, R1 is butyl, R2 is H, R3 is phenyl, R4 is methyl, and R5 is H.

[0053] Aryl boron halide is Ar is phenyl, and R is bromo.

[0054] The preparation method comprises the following steps:

[0055] (1) 1 mL of dichloromethane, 0.054 mmol of phenyl diboron bromide, 0.27 mmol of α-butyl propenal and 0.405 mmol of α-methyl styrene are put into a reaction container, and the reaction is carried out at -20°C for 6 h;

[0056] (2) 0.16 mmol of triethylamine is added to the reaction system to quench the reaction, and a reaction mixture is obtained;

[0057] (3) The reaction mixture is left to room temperature, low-boiling substances are removed by distillation under reduced pressure, and then the purified 3,4-dihydropyrane derivative is obtained by column chromatography purification.

[0058] The 3,4-dihydropyran derivative prepared in this example has the structural formula The mass is 48.5 mg, and the yield is 78%. The characterization data of the 3,4-dihydropyran derivative are as follows:

[0059] TLC: R f 0.5 (ethyl acetate / hexane = 1:20) [KMnO4, UV];

[0060] 1 H NMR (500 MHz, CDCI3) δ 7.37 - 7.35 (m, 2H), 7.33 - 7.30 (m, 2H), 7.23 - 7.20 (m, 1H), 6.29 (s, 1H), 2.20 - 2.15 (m, 1H), 1.93 - 1.88 (m, 1H), 1.85 - 1.80 (m, 3H), 1.65 - 1.59 (m, 1H), 1.49 (s, 3H), 1.27 - 1.20 (m, 2H), 1.19 - 1.11 (m, 2H), 0.82 (t, J = 7.2 Hz, 3H);

[0061] 13 C NMR (126 MHz, CDCI3) δ 146.17, 137.30, 128.20, 126.61, 124.90, 112.17, 76.87, 33.34, 32.55, 30.07, 29.22, 22.09, 21.55, 14.01;

[0062] IR (neat) 3063, 2963, 2930, 1669, 1451, 1163, 1140, 1073, 765, 702 cm -1 ;

[0063] HRMS (ESI) exact mass calcd. for C 16 H 22 O: m / z 253.1563 ([M+Na] + ), found: m / z 253.1565 ([M+Na] + ).

[0064] Example 4

[0065] The unactivated propenals are a-benzyl propenals, the weakly polar olefins are a-methyl styrene, R1 is benzyl, R2 is H, R3 is phenyl, R4 is methyl, and R5 is H.

[0066] The aryl boron halide is Ar is phenyl, and R is chloro.

[0067] The preparation method comprises the following steps:

[0068] (1) 1 mL of dichloromethane, 0.054 mmol of phenyl boron dichloride, 0.27 mmol of α-benzyl propenal and 0.405 mmol of α-methyl styrene are put into a reaction container, and the reaction is carried out at -20°C for 6 h;

[0069] (2) 0.16 mmol of triethylamine is added to the reaction system to quench the reaction, and a reaction mixture is obtained;

[0070] (3) The reaction mixture is left to room temperature, low-boiling substances are removed by distillation under reduced pressure, and then purified by column chromatography to obtain a purified 3,4-dihydropyrane derivative.

[0071] The 3,4-dihydropyrane derivative prepared in the example has the structural formula The mass is 68.5 mg, and the yield is 96%. The characterization data of the 3,4-dihydropyrane derivative are as follows:

[0072] TLC: R f 0.6 (ethyl acetate / hexane = 1:20) [KMnO4, UV];

[0073] 1 H NMR (500 MHz, CDCl3) δ 7.39-7.37 (m, 2H), 7.34-7.31 (m, 2H), 7.26-7.23 (m, 1H), 7.20-7.17 (m, 2H), 7.14-7.11 (m, 1H), 7.01 (d, J = 7.0 Hz, 2H), 6.45 (s, 1H), 3.17-3.10 (m, 2H), 2.19-2.14 (m, 1H), 1.92-1.86 (m, 1H), 1.75-1.70 (m, 1H), 1.58-1.51 (m, 1H), 1.50 (s, 3H);

[0074] 13 C NMR (126 MHz, CDCl3) δ 145.99, 140.40, 139.05, 128.57, 128.30, 128.26, 126.73, 125.98, 124.94, 111.62, 77.22, 39.29, 33.14, 29.30, 21.41;

[0075] IR (neat) 3065, 2977, 2926, 1671, 1500, 1448, 1267, 1134, 738, 697 cm -1 ;

[0076] HRMS (ESI) exact mass calcd. for C 19 H 20 O: m / z 265.1587 ([M+H] + ), found: m / z 265.1586 ([M+H] + ).

[0077] Example 5

[0078] Unactivated propenal is α-isopropyl propenal, weakly polar olefin α-methyl styrene, R1 is isopropyl, R2 is H, R3 is phenyl, R4 is methyl, and R5 is H.

[0079] Aryl boron halide is Ar is phenyl, and R is chloro.

[0080] The preparation method comprises the following steps:

[0081] (1) 1 mL of dichloromethane, 0.054 mmol of phenyl boron dichloride, 0.27 mmol of α-isopropyl propenal and 0.405 mmol of α-methyl styrene are put into a reaction container, and the reaction is carried out at -20 °C overnight;

[0082] (2) 0.11 mmol of triethylamine is added to the reaction system to quench the reaction, and a reaction mixture is obtained;

[0083] (3) The reaction mixture is left to room temperature, low-boiling substances are removed by distillation under reduced pressure, and then column chromatography is used for purification to obtain a purified 3,4-dihydropyrane derivative.

[0084] The structure of the 3,4-dihydropyrane derivative prepared in the embodiment is as follows: The mass is 49.6 mg, and the yield is 85%. The characterization data of the 3,4-dihydropyrane derivative are as follows:

[0085] TLC: R f 0.7 (ethyl acetate / hexane = 1:20) [KMnO4, UV];

[0086] 1 H NMR (500 MHz, CDCl3) δ 7.37-7.35 (m, 2H), 7.33-7.30 (m, 2H), 7.24-7.20 (m, 1H), 6.33 (s, 1H), 2.17-2.09 (m, 2H), 1.92-1.84 (m, 2H), 1.65-1.59 (m, 1H), 1.49 (s, 3H), 0.91 (dd, J = 16.2, 6.9 Hz, 6H);

[0087] 13 C NMR (126 MHz, CDC13) δ 146.23, 136.11, 128.17, 126.59, 124.84, 117.83, 76.98, 33.52, 31.29, 28.90, 21.71, 21.53, 18.92;

[0088] IR (neat) 3061, 2959, 2924, 1663, 1446, 1191, 1163, 1118, 763, 700 cm -1 ;

[0089] HRMS (ESI) exact mass calcd. for C 15 H 20 O: m / z 239.1406 ([M+Na] + ), found: m / z 239.1409 ([M+Na] + ).

[0090] Example 6

[0091] Unactivated propenal is a-cyclohexylpropenal, weakly polar olefin a-methylstyrene, R1 is cyclohexyl, R2 is H, R3 is phenyl, R4 is methyl, and R5 is H.

[0092] Aryl boron halide is Ar is phenyl and R is chloro.

[0093] The preparation method comprises the following steps:

[0094] (1) 1 mL of dichloromethane, 0.054 mmol of phenyl boron dichloride, 0.27 mmol of a-cyclohexylpropenal and 0.405 mmol of a-methylstyrene are put into a reaction container, and the reaction is carried out at -20°C overnight;

[0095] (2) 0.11 mmol of triethylamine is added to the reaction system to quench the reaction, and a reaction mixture is obtained;

[0096] (3) The reaction mixture is left to room temperature, low-boiling substances are removed by distillation under reduced pressure, and then the purified 3,4-dihydropyrane derivative is obtained by column chromatography purification.

[0097] The structure of the 3,4-dihydropyrane derivative prepared in this example is The mass is 49.1 mg, and the yield is 71%. The characterization data of the 3,4-dihydropyrane derivative are as follows:

[0098] TLC: R f0.7 (ethyl acetate / hexane = 1:20) [KMn04, UV];

[0099] 1 H NMR (500 MHz, CDC13) δ 7.36 - 7.34 (m, 2H), 7.32 - 7.29 (m, 2H), 7.23 - 7.20 (m, 1H), 6.32 (s, 1H), 2.16 - 2.11 (m, 1H), 1.91 - 1.84 (m, 2H), 1.73 - 1.67 (m, 3H), 1.64 - 1.51 (m, 4H), 1.48 (s, 3H), 1.25 - 1.17 (m, 2H), 1.13 - 1.02 (m, 3H);

[0100] 13 C NMR (126 MHz, CDC13) δ 146.20, 136.53, 128.15, 126.57, 124.86, 117.47, 76.99, 41.65, 33.59, 32.22, 32.06, 28.96, 26.77, 26.46, 19.70;

[0101] IR (neat) 3026, 2928, 2855, 1667, 1448, 1163, 1146, 1118, 765, 697 cm -1 ;

[0102] HRMS (ESI) exact mass calcd. for C 18 H 24 O: m / z 279.1719 ([M+Na] + ), found: m / z 279.1722 ([M+Na] + ).

[0103] Example 7

[0104] Unactivated propenal is α-methyl-β-methylacrylaldehyde, weakly polar olefin α-methylstyrene, R1 is methyl, R2 is methyl, R3 is phenyl, R4 is methyl, and R5 is H.

[0105] Aryl boron halide is Ar is phenyl and R is chloro.

[0106] The method of preparation comprises the following steps:

[0107] (1) Put 1 mL of dichloromethane, 0.081 mmol of phenyl boron dichloride, 0.27 mmol of α-methyl-β-methylacrylaldehyde, and 0.405 mmol of α-methylstyrene into a reaction vessel, and react at 0°C for 3 days.

[0108] (2) The reaction was quenched by adding 0.2 mmol of triethylamine to the reaction system to obtain a reaction mixture;

[0109] (3) The reaction mixture was left to room temperature, and low-boiling substances were removed by distillation under reduced pressure, and then purified by column chromatography to obtain the purified 3,4-dihydropyrane derivative.

[0110] The 3,4-dihydropyrane derivative prepared in this example has the structural formula The mass was 26.7 mg, and the yield was 49%. The characterization data of the 3,4-dihydropyrane derivative are as follows:

[0111] TLC: R f 0.8 (ethyl acetate / hexane = 1:20) [KMnO4, UV];

[0112] 1 H NMR (500 MHz, CDCI3) δ 7.44-7.42 (m, 2H), 7.34-7.30 (m, 2H), 7.24-7.21 (m, 1H), 6.23 (s, 1H), 2.31-2.23 (m, 1H), 2.02 (dd, J = 13.6, 6.0 Hz, 1H), 1.63-1.58 (m, 1H), 1.58-1.56 (m, 3H), 1.51 (s, 3H), 0.94 (d, J = 7.0 Hz, 3H);

[0113] 13 C NMR (126 MHz, CDCI3) δ 147.63, 136.55, 128.23, 126.74, 124.59, 111.21, 76.75, 44.24, 27.96, 24.74, 18.48, 15.74;

[0114] IR (neat) 3063, 2973, 2926, 1665, 1448, 1251, 1183, 1146, 761, 704 cm -1 ;

[0115] HRMS (ESI) exact mass calcd. for C 14 H 18 O: m / z 225.1250 ([M+Na] + ), found: m / z 225.1253 ([M+Na] + ).

[0116] Example 8

[0117] Unactivated acrolein is α-phenyl-β-methylacrolein, weakly polarized olefin α-methylstyrene, R1 is phenyl, R2 is methyl, R3 is phenyl, R4 is methyl, and R5 is H.

[0118] Aryl boron halide is Ar is phenyl, and R is chloro.

[0119] The preparation method comprises the following steps:

[0120] (1) 1 mL of acetonitrile, 0.108 mmol of phenyl boron dichloride, 0.27 mmol of α-methyl-β-methylacrolein and 0.405 mmol of α-methylstyrene are put into a reaction container, and the reaction is carried out at -20 °C for 18 h;

[0121] (2) 0.31 mmol of triethylamine is added to the reaction system to quench the reaction, and a reaction mixture is obtained;

[0122] (3) The reaction mixture is left to room temperature, low-boiling substances are removed by distillation under reduced pressure, and then purified by column chromatography to obtain a purified 3,4-dihydropyrane derivative.

[0123] The 3,4-dihydropyrane derivative prepared in the embodiment has the structural formula The mass is 32.1 mg, and the yield is 45%. The characterization data of the 3,4-dihydropyrane derivative are as follows:

[0124] TLC: R f 0.5 (ethyl acetate / hexane = 1:50) [KMnO4, UV];

[0125] 1 H NMR (500 MHz, CDCl3) δ 7.49-7.47 (m, 2H), 7.38-7.34 (m, 2H), 7.32-7.29 (m, 2H), 7.26-7.23 (m, 3H), 7.18 (s, 1H), 6.70 (d, J = 1.5 Hz, 1H), 2.97-2.89 (m, 1H), 2.23 (dd, J = 13.8, 6.2 Hz, 1H), 1.85 (dd, J = 13.8, 9.2 Hz, 1H), 1.63 (s, 3H), 0.82 (d, J = 6.9 Hz, 3H); 13 CNMR (126 MHz, CDCl3) δ 146.85, 140.32, 139.10, 128.40, 128.35, 126.97, 126.68, 125.97, 124.66, 118.39, 77.55, 43.78, 26.02, 25.69, 19.34;

[0126] IR (neat) 3063, 2983, 2930, 1640, 1502, 1444, 1193, 1171, 761, 695 cm -1 ;

[0127] HRMS (ESI) exact mass calcd. for C 19 H 20 O: m / z 287.1406 ([M+Na] + ), found: m / z 287.1409 ([M+Na] + ).

[0128] Example 9

[0129] Unactivated propenal is α-phenyl-β-ethyl propenal, weakly polar olefin α-methyl styrene, R1 is phenyl, R2 is ethyl, R3 is phenyl, R4 is methyl, and R5 is H.

[0130] Aryl boron halide is Ar is phenyl, and R is chloro.

[0131] The preparation method comprises the following steps:

[0132] (1) 1 mL of dichloromethane, 0.108 mmol of phenyl boron dichloride, 0.27 mmol of α-cyclohexyl propenal and 0.405 mmol of α-methyl styrene are put into a reaction container, and the reaction is carried out at -20 °C for 3 days;

[0133] (2) 0.3 mmol of triethylamine is added to the reaction system to quench the reaction, and a reaction mixture is obtained;

[0134] (3) The reaction mixture is left to room temperature, low-boiling substances are removed by distillation under reduced pressure, and then the purified 3,4-dihydropyrane derivative is obtained by column chromatography purification.

[0135] The structure of the 3,4-dihydropyrane derivative prepared in the embodiment is as follows: The mass is 42.1 mg, and the yield is 56%. The characterization data of the 3,4-dihydropyrane derivative are as follows:

[0136] TLC: R f 0.5 (ethyl acetate / hexane = 1:50) [KMnO4, UV];

[0137] 1H NMR (500 MHz, CDC13) δ 7.50 - 7.48 (m, 2H), 7.39 - 7.36 (m, 2H), 7.32 - 7.26 (m, 3H), 7.24 - 7.18 (m, 3H), 6.69 (d, J = 1.6 Hz, 1H), 2.79 - 2.73 (m, 1H), 2.18 (dd, J = 13.8, 6.3 Hz, 1H), 1.88 (dd, J = 13.8, 9.5 Hz, 1H), 1.63 (s, 3H), 1.51 - 1.46 (m, 1H), 0.99 - 0.90 (m, 1H), 0.74 (t, J = 7.4 Hz, 3H);

[0138] 13 C NMR (126 MHz, CDC13) δ 147.09, 140.99, 139.27, 128.41, 128.36, 126.99, 126.73, 125.96, 124.59, 117.78, 77.60, 39.86, 32.29, 25.38, 25.11, 10.72;

[0139] IR (neat) 3059, 2969, 2930, 1638, 1267, 1191, 1169, 1132, 740, 697 cm -1 ;

[0140] HRMS (ESI) exact mass calcd. for C 20 H 22 O: m / z 279.1743 ([M+H] + ), found: m / z 279.1741 ([M+H] + ).

[0141] Example 10

[0142] The unactivated acrolein is a-(3-chloro-n-propyl)acrolein, the weakly polar olefin is a-methylstyrene, R1is 3-chloro-n-propyl, R2is H, R3is phenyl, R4is methyl, and R5is H.

[0143] The aryl boron halide is Ar is phenyl and R is chloro.

[0144] The method of preparation comprises the following steps:

[0145] (1) Into a reaction vessel was charged 1 mL of 1,2-dichloroethane, 0.054 mmol of phenylboron dichloride, 0.27 mmol of a-cyclohexylacrolein, and 0.405 mmol of a-methylstyrene, and reacted for 15 h at -20 °C;

[0146] (2) The reaction was quenched by adding 0.11 mmol of triethylamine to the reaction system, and a reaction mixture was obtained;

[0147] (3) The reaction mixture was left to room temperature, and low-boiling substances were removed by distillation under reduced pressure, and then purified by column chromatography to obtain the purified 3,4-dihydropyrane derivative.

[0148] The 3,4-dihydropyrane derivative prepared in this example has the structural formula The mass was 54.8 mg, and the yield was 81%. The characterization data of the 3,4-dihydropyrane derivative are as follows:

[0149] TLC: R f 0.6 (ethyl acetate / hexane = 1:20) [KMnO4, UV];

[0150] 1 H NMR (500 MHz, Chloroform-d) δ 7.36-7.30 (m, 4H), 7.24-7.23 (m, 1H), 6.35 (s, 1H), 3.33-3.23 (m, 2H), 2.24-2.20 (m, 1H), 2.01-1.89 (m, 3H), 1.81-1.76 (m, 1H), 1.71-1.58 (m, 3H), 1.49 (s, 3H).

[0151] 13 C NMR (126 MHz, Chloroform-d) δ 145.7, 138.6, 128.3, 126.8, 124.8, 110.0, 77.2, 44.2, 33.0, 30.4, 29.9, 29.6, 21.4.

[0152] IR (neat) 3017, 2931, 2865, 1663, 1445, 1160, 1142, 1121, 778, 683 cm -1 ;

[0153] HRMS (ESI) exact mass calcd. for C 18 H 24 O: m / z 273.1017 ([M+Na] + ), found: m / z 279.11019 ([M+Na] + ).

[0154] Example 11

[0155] Unactivated acrolein is α-isopropylacrolein, weakly polarized olefin α-n-propylstyrene, R1 is isopropyl, R2 is H, R3 is phenyl, R4 is n-propyl, and R5 is H.

[0156] Aryl boron halide is Ar is phenyl, and R is chloro.

[0157] The preparation method comprises the following steps:

[0158] (1) 1 mL of dichloromethane, 0.054 mmol of phenyl boron dichloride, 0.27 mmol of α-isopropylacrolein and 0.405 mmol of α-n-propylstyrene are put into a reaction container, and the reaction is carried out at -20 °C for 4.5 h;

[0159] (2) 0.15 mmol of triethylamine is added to the reaction system to quench the reaction, and a reaction mixture is obtained;

[0160] (3) The reaction mixture is left to room temperature, low-boiling substances are removed by distillation under reduced pressure, and then the purified 3,4-dihydropyrane derivative is obtained by column chromatography purification.

[0161] The 3,4-dihydropyrane derivative prepared in the embodiment has the structural formula The mass is 52.7 mg, and the yield is 80%. The characterization data of the 3,4-dihydropyrane derivative are as follows:

[0162] TLC: R f 0.7 (ethyl acetate / hexane = 1:20) [KMnO4, UV];

[0163] 1 H NMR (500 MHz, CDCl3) δ 7.30 (d, J = 4.2 Hz, 4H), 7.23-7.19 (m, 1H), 6.33 (s, 1H), 2.17-2.06 (m, 2H), 1.94-1.88 (m, 1H), 1.84-1.74 (m, 2H), 1.72-1.66 (m, 1H), 1.58-1.51 (m, 1H), 1.39-1.28 (m, 1H), 1.08-0.97 (m, 1H), 0.87 (dd, J = 17.7, 6.8 Hz, 6H), 0.80 (t, J = 7.4 Hz, 3H);

[0164] 13C NMR (126 MHz, CDCI3) δ 144.59, 136.09, 127.97, 126.38, 125.49, 118.16, 79.48, 44.61, 32.00, 31.28, 21.77, 21.44, 18.69, 16.70, 14.55;

[0165] IR (neat) 3061, 2957, 2873, 1667, 1448, 1179, 1120, 1057, 769, 702 cm -1 ;

[0166] HRMS (ESI) exact mass calcd. for C 17 H 24 O: m / z 267.1719 ([M+Na] + ), found: m / z 267.1717 ([M+Na] + ).

[0167] Example 12

[0168] Unactivated propenal is α-isopropyl propenal, weakly polar olefin is α-n-heptyl styrene, R1 is isopropyl, R2 is H, R3 is phenyl, R4 is n-heptyl, and R5 is H.

[0169] Aryl boron halide is Ar is phenyl, and R is chloro.

[0170] The preparation method comprises the following steps:

[0171] (1) 1 mL of dichloromethane, 0.054 mmol of phenyl boron dichloride, 0.27 mmol of α-isopropyl propenal and 0.405 mmol of α-n-heptyl styrene are put into a reaction container, and the reaction is carried out at -20°C overnight;

[0172] (2) 0.15 mmol of triethylamine is added to the reaction system to quench the reaction, and a reaction mixture is obtained;

[0173] (3) The reaction mixture is left to room temperature, low-boiling substances are removed by distillation under reduced pressure, and then the purified 3,4-dihydropyrane derivative is obtained by column chromatography purification.

[0174] The structure of the 3,4-dihydropyrane derivative prepared in the embodiment is The mass is 73.0 mg, and the yield is 90%. The characterization data of the 3,4-dihydropyrane derivative are as follows:

[0175] TLC: R f0.8 (ethyl acetate / hexane = 1 :20) [KMn04, UV];

[0176] 1 H NMR (500 MHz, CDC13) δ 7.32 - 7.29 (m, 4H), 7.23 - 7.19 (m, 1H), 6.33 (s, 1H), 2.16 - 2.06 (m, 2H), 1.94 - 1.89 (m, 1H), 1.84 - 1.67 (m, 3H), 1.58 - 1.51 (m, 1H), 1.36 - 1.28 (m, 1H), 1.26 - 1.14 (m, 7H), 1.05 - 0.97 (m, 1H), 0.89 (d, J = 6.8 Hz, 3H), 0.84 (dd, J = 15.2, 7.1 Hz, 6H);

[0177] 13 C NMR (126 MHz, CDC13) δ 144.66, 136.11, 127.98, 126.37, 125.49, 118.17, 79.48, 42.27, 32.01, 31.98, 31.29, 30.10, 29.33, 23.35, 22.78, 21.77, 21.45, 18.71, 14.22;

[0178] IR (neat) 3065, 2928, 2861, 1669, 1469, 1448, 1173, 1120, 736, 702 cm -1 ;

[0179] HRMS (ESI) exact mass calcd. for C 21 H 32 O: m / z 323.2345 ([M+Na] + ), found: m / z 323.2346 ([M+Na] + ).

[0180] Example 13

[0181] Unactivated propenals are a-isopropyl propenals, weakly polar olefins a-methyl-p-fluorostyrene, R1 is isopropyl, R2 is H, R3 is methyl-p-fluorophenyl, R4 is methyl, R5 is H.

[0182] Aryl boronic acids are Ar is 1-naphthyl, R is chloro.

[0183] The method of preparation comprises the steps of:

[0184] (1) 1 mL of dichloromethane, 0.054 mmol of 1-naphthyl boron dichloride, 0.27 mmol of α-isopropyl propyl aldehyde and 0.405 mmol of α-methyl-p-fluorostyrene were put into a reaction vessel, and reacted at 0°C for 10 h;

[0185] (2) 0.15 mmol of triethylamine was added to the reaction system to quench the reaction, and a reaction mixture was obtained;

[0186] (3) The reaction mixture was left to room temperature, and low-boiling substances were removed by distillation under reduced pressure, and then purified by column chromatography to obtain a purified 3,4-dihydropyrane derivative.

[0187] The 3,4-dihydropyrane derivative prepared in this example had a structural formula of The mass was 60.1 mg, and the yield was 95%. The characterization data of the 3,4-dihydropyrane derivative were as follows:

[0188] TLC: R f 0.8 (ethyl acetate / hexane = 1:20) [KMnO4, UV];

[0189] 1 H NMR (500 MHz, CDCl3) δ 7.34-7.30 (m, 2H), 7.01-6.97 (m, 2H), 6.30 (s, 1H), 2.15-2.08 (m, 2H), 1.91-1.85 (m, 2H), 1.65-1.57 (m, 1H), 1.47 (s, 3H), 0.91 (dd, J = 15.4, 6.9 Hz, 6H);

[0190] 13 C NMR (126 MHz, CDCl3) δ 161.69 (d, J CF = 244.4 Hz), 141.96 (d, J CF = 2.5 Hz), 136.01, 126.56 (d, J CF = 7.6 Hz), 117.98, 114.92 (d, J CF = 21.4 Hz), 76.65, 33.53, 31.28, 29.01, 21.71, 21.51, 18.88;

[0191] IR (neat) 3069, 2965, 2928, 1669, 1516, 1455, 1232, 1161, 1116, 832, 806, 726 cm -1 ;

[0192] HRMS (ESI) exact mass calcd. for C 15 H 19 FO:m / z 257.1312([M+Na] + ), found:m / z257.1314([M+Na] + ).

[0193] Example 14

[0194] Unactivated propenal is α-isopropylpropenal, weakly polarized olefin is α-methyl-p-chlorostyrene, R1 is isopropyl, R2 is H, R3 is methyl-p-chlorophenyl, R4 is methyl, and R5 is H.

[0195] Aryl boron halide is Ar is 1-naphthyl, and R is chloro.

[0196] The preparation method comprises the following steps:

[0197] (1) 1 mL of dichloromethane, 0.054 mmol of 1-naphthyl boron dichloride, 0.27 mmol of α-isopropylpropenal and 0.405 mmol of α-methyl-p-chlorostyrene are put into a reaction container, and the reaction is carried out at -20 °C for 5 h;

[0198] (2) 0.15 mmol of triethylamine is added to the reaction system to quench the reaction, and a reaction mixture is obtained;

[0199] (3) The reaction mixture is left to room temperature, low-boiling substances are removed by distillation under reduced pressure, and then the purified 3,4-dihydropyrane derivative is obtained by column chromatography purification.

[0200] The structure of the 3,4-dihydropyrane derivative prepared in the embodiment is as follows: The mass is 50.0 mg, and the yield is 74%. The characterization data of the 3,4-dihydropyrane derivative are as follows:

[0201] TLC:R f 0.9 (ethyl acetate / hexane = 1:20) [KMnO4, UV];

[0202] 1 H NMR (500 MHz, CDCl3) δ 7.30-7.26 (m, 4H), 6.30 (s, 1H), 2.16-2.08 (m, 2H), 1.90-1.85 (m, 2H), 1.63-1.56 (m, 1H), 1.46 (s, 3H), 0.91 (dd, J = 14.9, 6.9 Hz, 6H);

[0203] 13C NMR (126 MHz, CDCI3) δ 144.80, 135.98, 132.35, 128.33, 126.44, 118.05, 76.66, 33.36, 31.27, 28.99, 21.71, 21.50, 18.85;

[0204] IR (neat) 3079, 2959, 2930, 1665, 1491, 1275, 1167, 1118, 1095, 1010, 828, 734 cm -1 ; HRMS (ESI) exact mass calcd. for C 15 H 19 ClO: m / z 273.1017 ([M+Na + ), found: m / z 273.1017 ([M+Na + ).

[0205] Example 14

[0206] Unactivated propenal is α-isopropyl propenal, weakly polar olefin is α-methyl-p-trifluoromethyl styrene, R1 is isopropyl, R2 is H, R3 is methyl-p-trifluoromethyl phenyl, R4 is methyl, and R5 is H.

[0207] Aryl boron halide is aryl boron halide is Ar is phenyl, and R is chloro.

[0208] The preparation method comprises the following steps:

[0209] (1) putting 1 mL of dichloromethane, 0.108 mmol of phenyl boron dichloride, 0.27 mmol of α-isopropyl propenal and 0.405 mmol of α-methyl-p-trifluoromethyl styrene into a reaction container, and reacting at 0°C for 1 day;

[0210] (2) adding 0.3 mmol of triethylamine to the reaction system to quench the reaction, to obtain a reaction mixture;

[0211] (3) placing the reaction mixture to room temperature, removing low-boiling substances under reduced pressure, and then purifying through column chromatography to obtain a purified 3,4-dihydropyrane derivative.

[0212] The structure of the 3,4-dihydropyrane derivative prepared in the example is The mass is 46.0 mg, and the yield is 60%. The characterization data of the 3,4-dihydropyrane derivative are as follows:

[0213] TLC: R f0.8 (ethyl acetate / hexane = 1 :20) [KMn04, UV];

[0214] 1 H NMR (500 MHz, CDC13) δ 7.57 (d, J = 8.3 Hz, 2H), 7.47 (d, J = 8.2 Hz, 2H), 6.33 (s, 1H), 2.18 - 2.10 (m, 2H), 1.95 - 1.87 (m, 2H), 1.62 - 1.55 (m, 1H), 1.49 (s, 3H), 0.91 (dd, J = 16.1, 6.9 Hz, 6H);

[0215] 13 C NMR (126 MHz, CDC13) δ 150.32, 135.97, 129.98 (q, J CF = 32.8 Hz), 125.35, 125.22 (q, J CF = 3.8 Hz), 124.4 (q, J CF = 273.4 Hz), 118.19, 76.81, 33.32, 31.26, 28.91, 21.68, 21.48, 18.84; IR (neat) 3073, 2965, 2932, 1669, 1410, 1328, 1116, 1081, 840, 708 cm -1 ;

[0216] HRMS (ESI) exact mass calcd. for C 16 H 19 FO: m / z 285.1461 ([M+H] + ), found: m / z 285.1459 ([M+H] + ).

[0217] Example 15

[0218] Unactivated propenal is a-isopropyl propenal, weakly polar olefin is p-methoxystyrene, R1 is isopropyl, R2 is H, R3 is p-methoxyphenyl, R4 is H, R5 is H.

[0219] Aryl boron halide is aryl boron halide is Ar is 3,5-dimethylphenyl, R is bromo.

[0220] The method of preparation comprises the steps of:

[0221] (1) 1 mL of dichloromethane, 0.054 mmol of 3,5-dichlorophenyl diboronic acid, 0.27 mmol of α-isopropylacrolein and 0.405 mmol of p-methoxyphenylstyrene were put into a reaction vessel and reacted at 0°C for 5 h;

[0222] (2) 0.15 mmol of triethylamine was added to the reaction system to quench the reaction, and a reaction mixture was obtained;

[0223] (3) The reaction mixture was left to room temperature, low boiling point substances were removed by distillation under reduced pressure, and then purified by column chromatography to obtain a purified 3,4-dihydropyrane derivative.

[0224] The 3,4-dihydropyrane derivative prepared in this example has a structural formula of The mass was 38.4 mg, and the yield was 50%. The characterization data of the 3,4-dihydropyrane derivative are as follows:

[0225] TLC: R f 0.7 (ethyl acetate / hexane = 1:20) [KMnO4, UV];

[0226] 1 H NMR (500 MHz, CDCl3) δ 7.28 (d, J = 8.5 Hz, 2H), 6.88 (d, J = 8.5 Hz, 2H), 6.38 (s, 1H), 4.66 (d, J = 10.5 Hz, 1H), 3.80 (s, 3H), 2.24-2.17 (m, 2H), 2.05-1.87 (m, 3H), 1.03 (t, J = 6.8 Hz, 6H);

[0227] 13 C NMR (126 MHz, CDCl3) δ 159.21, 138.01, 134.51, 127.37, 118.34, 113.89, 76.63, 55.40, 31.37, 30.27, 21.97, 21.48, 21.43;

[0228] IR (neat) 3060, 2966, 2921, 1669, 1524, 1268, 1251, 1180, 735, 700 cm -1 ;

[0229] HRMS (ESI) exact mass calcd. for C 15 H 20 O2: m / z 233.1536 ([M+H] + ), found: m / z 233.1533 ([M+H] + ).

[0230] Example 16

[0231] Unactivated propenal is α-isopropyl propenal, weakly polarized olefin α-methyl-p-methylstyrene, R1 is isopropyl, R2 is H, R3 is methyl-p-methylphenyl, R4 is methyl, and R5 is H.

[0232] Aryl boron halide is aryl boron halide is Ar is phenyl, and R is chloro.

[0233] The preparation method comprises the following steps:

[0234] (1) 1 mL of dichloromethane, 0.054 mmol of phenyl boron dichloride, 0.27 mmol of α-isopropyl propenal and 0.405 mmol of α-methyl-p-methylstyrene are put into a reaction container, and the reaction is carried out at -20 °C for 40 minutes;

[0235] (2) 0.15 mmol of triethylamine is added to the reaction system to quench the reaction, and a reaction mixture is obtained;

[0236] (3) The reaction mixture is left to room temperature, low-boiling substances are removed by distillation under reduced pressure, and then purified by column chromatography to obtain a purified 3,4-dihydropyrane derivative.

[0237] The 3,4-dihydropyrane derivative prepared in the embodiment has the structural formula The mass is 50.3 mg, and the yield is 81%. The characterization data of the 3,4-dihydropyrane derivative are as follows:

[0238] TLC: R f 0.8 (ethyl acetate / hexane = 1:20) [KMnO4, UV];

[0239] 1 H NMR (500 MHz, CDCl3) δ 7.25-7.23 (m, 2H), 7.12 (d, J = 8.0 Hz, 2H), 6.32 (s, 1H), 2.32 (s, 3H), 2.14-2.09 (m, 2H), 1.90-1.84 (m, 2H), 1.66-1.60 (m, 1H), 1.47 (s, 3H), 0.92 (dd, J = 14.7, 6.9 Hz, 6H);

[0240] 13C NMR (126 MHz, CDCI3) δ 143.34, 136.16, 136.06, 128.87, 124.76, 117.71, 76.89, 33.57, 31.31, 28.90, 21.72, 21.57, 21.12, 18.98;

[0241] IR (neat) 3024, 2967, 2928, 1667, 1453, 1193, 1167, 1114, 818, 734 cm -1 ;

[0242] HRMS (ESI) exact mass calcd. for C 16 H 22 O: m / z 253.1563 ([M+Na] + ), found: m / z 253.1558 ([M+Na] + ).

[0243] Example 17

[0244] Unactivated propenal is alpha-isopropyl propenal, weakly polar olefin alpha-methyl-m-methylstyrene, R1 is isopropyl, R2 is H, R3 is methyl-m-methylphenyl, R4 is methyl, and R5 is H.

[0245] Aryl boron halide is aryl boron halide is Ar is phenyl, and R is chloro.

[0246] The preparation method comprises the following steps:

[0247] (1) putting 1 mL of dichloromethane, 0.054 mmol of phenyl boron dichloride, 0.27 mmol of alpha-isopropyl propenal and 0.405 mmol of alpha-methyl-m-methylstyrene into a reaction container, and reacting at -20°C for 5 h;

[0248] (2) adding 0.15 mmol of triethylamine to the reaction system to quench the reaction, to obtain a reaction mixture;

[0249] (3) placing the reaction mixture to room temperature, removing low-boiling substances under reduced pressure, and then purifying by column chromatography to obtain a purified 3,4-dihydropyrane derivative.

[0250] The structure of the 3,4-dihydropyrane derivative prepared in the embodiment is The mass is 37.9 mg, and the yield is 61%. The characterization data of the 3,4-dihydropyrane derivative are as follows:

[0251] TLC: R f0.7 (ethyl acetate / hexane = 1 :20) [KMn04, UV];

[0252] 1 H NMR (500 MHz, CDC13) δ 7.22 - 7.14 (m, 3H), 7.03 (d, J = 7.3 Hz, 1H), 6.33 (s, 1H), 2.35 (s, 3H), 2.16 - 2.09 (m, 2H), 1.91 - 1.85 (m, 2H), 1.68 - 1.60 (m, 1H), 1.48 (s, 3H), 0.92 (dd, J = 14.5, 6.9 Hz, 6H);

[0253] 13 C NMR (126 MHz, CDC13) δ 146.31, 137.64, 136.14, 128.07, 127.34, 125.53, 121.88, 117.72, 76.93, 33.64, 31.32, 28.58, 21.79, 21.70, 21.61, 18.96;

[0254] IR (neat) 3046, 2966, 2926, 1666, 1456, 1194, 1118, 1050, 788, 706 cm -1 ;

[0255] HRMS (ESI) exact mass calcd. for C 16 H 22 O: m / z 231.1743 ([M+H] + ), found: m / z 231.1738 ([M+H] + ).

[0256] Example 18

[0257] Unactivated propenals are a-isopropyl propenals, weakly polar olefins a-methyl-o- methylstyrene, R1 is isopropyl, R2 is H, R3 is methyl-o-methylphenyl, R4 is methyl, R5 is H.

[0258] Aryl boron halides are aryl boron halides are Ar is phenyl, R is chloro.

[0259] The method of preparation comprises the following steps:

[0260] (1) Into a reaction vessel was charged 1 mL of dichloromethane, 0.054 mmol of phenyl boron dichloride, 0.27 mmol of a-isopropyl propenals, and 0.405 mmol of a-methyl-o-methylstyrene, and reacted at 0 °C for 48 h;

[0261] (2) The reaction was quenched by adding 0.15 mmol of triethylamine to the reaction system to obtain a reaction mixture;

[0262] (3) The reaction mixture was left to room temperature, and low-boiling substances were removed by distillation under reduced pressure, and then purified by column chromatography to obtain the purified 3,4-dihydropyrane derivative.

[0263] The 3,4-dihydropyrane derivative prepared in this example has the structural formula The mass was 40.4 mg, and the yield was 65%. The characterization data of the 3,4-dihydropyrane derivative are as follows:

[0264] TLC: R f 0.8 (ethyl acetate / hexane = 1:20) [KMnO4, UV];

[0265] 1 H NMR (500 MHz, CDCl3) δ 7.38-7.35 (m, 1H), 7.15-7.13 (m, 3H), 6.26 (s, 1H), 2.48 (s, 3H), 2.39-2.34 (m, 1H), 2.17-2.09 (m, 1H), 1.97-1.91 (m, 1H), 1.89-1.84 (m, 1H), 1.81-1.75 (m, 1H), 1.55 (s, 3H), 0.92 (dd, J = 16.3, 6.8 Hz, 6H);

[0266] 13 C NMR (126 MHz, CDCl3) δ 143.31, 135.61, 135.41, 132.75, 126.95, 126.21, 125.70, 118.03, 77.96, 32.27, 31.27, 26.66, 22.38, 21.67, 19.13;

[0267] IR (neat) 3074, 2963, 2926, 1669, 1458, 1163, 1112, 1058, 757, 726 cm -1 ;

[0268] HRMS (ESI) exact mass calcd. for C 16 H 22 O: m / z 231.1743 ([M+H] + ), found: m / z 231.1739 ([M+H] + ).

[0269] Example 18

[0270] Unactivated propenal is α-isopropyl propenal, weakly polar olefin α-methyl-3,5-dimethylstyrene, R1 is isopropyl, R2 is H, R3 is methyl-3,5-dimethylphenyl, R4 is methyl, and R5 is H.

[0271] Aryl boron halide is aryl boron halide is Ar is phenyl, and R is chloro.

[0272] The preparation method comprises the following steps:

[0273] (1) 1 mL of dichloromethane, 0.054 mmol of phenyl boron dichloride, 0.27 mmol of α-isopropyl propenal and 0.405 mmol of α-methyl-3,5-dimethylstyrene are put into a reaction container, and the reaction is carried out at -20 °C for 4.5 h;

[0274] (2) 0.15 mmol of triethylamine is added to the reaction system to quench the reaction, and a reaction mixture is obtained;

[0275] (3) The reaction mixture is left to room temperature, low-boiling substances are removed by distillation under reduced pressure, and then column chromatography is used for purification, so that a purified 3,4-dihydropyrane derivative is obtained.

[0276] The 3,4-dihydropyrane derivative prepared in the embodiment has the structural formula The mass is 52.1 mg, and the yield is 79%. The characterization data of the 3,4-dihydropyrane derivative are as follows:

[0277] TLC: R f 0.8 (ethyl acetate / hexane = 1:20) [KMnO4, UV];

[0278] 1 H NMR (500 MHz, CDCl3) δ 6.97 (s, 2H), 6.86 (s, 1H), 6.32 (s, 1H), 2.31 (s, 6H), 2.18-2.05 (m, 2H), 1.92-1.84 (m, 2H), 1.68-1.61 (m, 1H), 1.47 (s, 3H), 0.93 (dd, J = 13.2, 6.9 Hz, 6H); 13 C NMR (126 MHz, CDCl3) δ 146.40, 137.53, 136.13, 128.24, 122.58, 117.59, 76.88, 33.74, 31.33, 28.26, 21.69, 21.67, 21.66, 18.97;

[0279] IR (neat) 3018, 2959, 2926, 1665, 1608, 1451, 1191, 1169, 1118, 848, 708 cm -1 ;

[0280] HRMS (ESI) exact mass calcd. for C 17 H 24 O: m / z 267.1719 ([M+Na] + ), found: m / z 267.1715 ([M+Na] + ).

[0281] Example 19

[0282] Unactivated propenal is α-isopropyl propenal, weakly polar olefin α-methyl-3,4-dimethylstyrene, R1 is isopropyl, R2 is H, R3 is methyl-3,4-dimethylphenyl, R4 is methyl, and R5 is H.

[0283] Aryl boron halide is aryl boron halide is Ar is phenyl, and R is chloro.

[0284] The preparation method comprises the following steps:

[0285] (1) 1 mL of dichloromethane, 0.054 mmol of phenyl boron dichloride, 0.27 mmol of α-isopropyl propenal and 0.405 mmol of α-methyl-3,4-dimethylstyrene are put into a reaction container, and the reaction is carried out at -20 °C for 4 h;

[0286] (2) 0.15 mmol of triethylamine is added to the reaction system to quench the reaction, and a reaction mixture is obtained;

[0287] (3) The reaction mixture is left to room temperature, low-boiling substances are removed by distillation under reduced pressure, and then the purified 3,4-dihydropyrane derivative is obtained by column chromatography purification.

[0288] The structure of the 3,4-dihydropyrane derivative prepared in the embodiment is The mass is 59.3 mg, and the yield is 90%. The characterization data of the 3,4-dihydropyrane derivative are as follows:

[0289] TLC: R f 0.8 (ethyl acetate / hexane = 1:20) [KMnO4, UV];

[0290] 1H NMR (500 MHz, CDC13) δ 7.12 (s, 1H), 7.09 - 7.06 (m, 2H), 6.32 (s, 1H), 2.24 (d, J = 11.5 Hz, 6H), 2.16 - 2.07 (m, 2H), 1.91 - 1.84 (m, 2H), 1.68 - 1.62 (m, 1H), 1.47 (s, 3H), 0.93 (dd, J = 13.7, 6.9 Hz, 6H);

[0291] 13 C NMR (126 MHz, CDC13) δ 143.90, 136.18, 136.16, 134.70, 129.45, 126.06, 122.21, 117.57, 76.79, 33.66, 31.32, 28.58, 21.70, 21.65, 20.14, 19.47, 19.00;

[0292] IR (neat) 3030, 2963, 2926, 1665, 1455, 1271, 1191, 1169, 1114, 1048, 824, 736 cm -1 ; HRMS (ESI) exact mass calcd. for C 17 H 24 O: m / z 245.1900 ([M+H] + ), found: m / z 245.1889 ([M+H] + ).

[0293] Example 20

[0294] Unactivated propenal is a-isopropyl propenal, weakly polar olefin is 2-naphthyl propene, R1 is isopropyl, R2 is H, R3 is 2-naphthyl, R4 is methyl, and R5 is H.

[0295] Aryl boron halide is aryl boron halide is Ar is phenyl and R is chloro.

[0296] The preparation method comprises the following steps:

[0297] (1) 1 mL of dichloromethane, 0.054 mmol of phenyl boron dichloride, 0.27 mmol of a-isopropyl propenal and 0.405 mmol of a-methyl-1-naphthalene vinyl are put into a reaction container, and the reaction is carried out at -20°C for 5 h;

[0298] (2) 0.15 mmol of triethylamine is added to the reaction system to quench the reaction, and a reaction mixture is obtained;

[0299] (3) The reaction mixture was left to room temperature, low-boiling substances were removed by distillation under reduced pressure, and then purified by column chromatography to obtain the purified 3,4-dihydropyrane derivative.

[0300] The 3,4-dihydropyrane derivative prepared in this example has the structural formula The mass was 59.6 mg, and the yield was 83%. The characterization data of the 3,4-dihydropyrane derivative are as follows:

[0301] TLC: R f 0.7 (ethyl acetate / hexane = 1:20) [KMnO4, UV];

[0302] 1 H NMR (500 MHz, CDCI3) δ 7.83 - 7.79 (m, 4H), 7.49 - 7.41 (m, 3H), 6.41 (s, 1H), 2.28 - 2.23 (m, 1H), 2.16 - 2.08 (m, 1H), 1.99 - 1.87 (m, 2H), 1.67 - 1.60 (m, 1H), 1.57 (s, 3H), 0.90 (dd, J = 20.4, 6.9 Hz, 6H);

[0303] 13 C NMR (126 MHz, CDCI3) δ 143.60, 136.14, 133.39, 132.43, 128.25, 127.92, 127.59, 125.96, 125.66, 123.52, 117.97, 77.12, 33.44, 31.30, 28.91, 21.72, 21.58, 18.99;

[0304] IR (neat) 3057, 2959, 2924, 1665, 1281, 1189, 1163, 1112, 818, 744 cm -1 ;

[0305] HRMS (ESI) exact mass calcd. for C 19 H 22 O: m / z 289.1563 ([M+Na] + ), found: m / z 289.1569 ([M+Na] + ).

[0306] Example 21

[0307] Unactivated acrolein is alpha-isopropylacrolein, weakly polarized olefin alpha-3-methyl-4-fluorostyrene, R1 is isopropyl, R2 is H, R3 is 3-methyl-4-fluorophenyl, R4 is methyl, and R5 is H.

[0308] Aryl boron halide is aryl boron halide is Ar is phenyl, and R is chloro.

[0309] The preparation method comprises the following steps:

[0310] (1) 1 mL of dichloromethane, 0.054 mmol of phenyl boron dichloride, 0.27 mmol of alpha-isopropylacrolein and 0.405 mmol of alpha-3-methyl-4-fluorostyrene are put into a reaction container, and the reaction is carried out at -20 °C for 5 h;

[0311] (2) 0.15 mmol of triethylamine is added to the reaction system to quench the reaction, and a reaction mixture is obtained;

[0312] (3) The reaction mixture is left to room temperature, low-boiling substances are removed by distillation under reduced pressure, and then the purified 3,4-dihydropyrane derivative is obtained by column chromatography purification.

[0313] The structure of the 3,4-dihydropyrane derivative prepared in the embodiment is The mass is 52.3 mg, and the yield is 78%. The characterization data of the 3,4-dihydropyrane derivative are as follows:

[0314] TLC: R f 0.8 (ethyl acetate / hexane = 1:20) [KMnO4, UV];

[0315] 1 H NMR (500 MHz, CDCl3) δ 7.16 (dd, J = 7.4, 2.1 Hz, 1H), 7.14-7.11 (m, 1H), 6.92 (t, J = 9.0 Hz, 1H), 6.30 (s, 1H), 2.26 (d, J = 1.7 Hz, 3H), 2.16-2.06 (m, 2H), 1.91-1.84 (m, 2H), 1.66-1.58 (m, 1H), 1.46 (s, 3H), 0.92 (dd, J = 14.4, 6.9 Hz, 6H);

[0316] 13 C NMR (126 MHz, CDCl3) δ 160.20 (d, J CF = 243.2 Hz), 141.71 (d, J CF = 2.5 Hz), 136.02, 127.99 (d, J CF= 5.0 Hz), 124.23 (d, J = 17.6 Hz), 123.76 (d, J = 7.6 Hz), 117.83, 114.53 (d, J = 21.4 Hz), 76.58, 33.59, 31.30, 28.74, 21.70, 21.57, 18.90, 14.89 (d, J = 2.5 Hz); CF = 5.0 Hz), 124.23 (d, J = 17.6 Hz), 123.76 (d, J = 7.6 Hz), 117.83, 114.53 (d, J = 21.4 Hz), 76.58, 33.59, 31.30, 28.74, 21.70, 21.57, 18.90, 14.89 (d, J = 2.5 Hz); CF = 5.0 Hz), 124.23 (d, J = 17.6 Hz), 123.76 (d, J = 7.6 Hz), 117.83, 114.53 (d, J = 21.4 Hz), 76.58, 33.59, 31.30, 28.74, 21.70, 21.57, 18.90, 14.89 (d, J = 2.5 Hz); CF = 5.0 Hz), 124.23 (d, J = 17.6 Hz), 123.76 (d, J = 7.6 Hz), 117.83, 114.53 (d, J = 21.4 Hz), 76.58, 33.59, 31.30, 28.74, 21.70, 21.57, 18.90, 14.89 (d, J = 2.5 Hz); CF = 5.0 Hz), 124.23 (d, J = 17.6 Hz), 123.76 (d, J = 7.6 Hz), 117.83, 114.53 (d, J = 21.4 Hz), 76.58, 33.59, 31.30, 28.74, 21.70, 21.57, 18.90, 14.89 (d, J = 2.5 Hz);

[0317] IR (neat) 3067, 2959, 2928, 1665, 1506, 1265, 1183, 1112, 822, 736 cm -1 ;

[0318] HRMS (ESI) exact mass calcd. for C 16 H 21 FO: m / z 249.1649 ([M+H] + ), found: m / z 249.1649 ([M+H] + ).

[0319] Example 22

[0320] Unactivated propenal is α-isopropyl propenal, weakly polar olefin α-phenyl styrene, R1 is isopropyl, R2 is H, R3 is phenyl, R4 is phenyl, and R5 is H.

[0321] Aryl boron halide is aryl boron halide is Ar is phenyl, and R is chloro.

[0322] The preparation method comprises the following steps:

[0323] (1) Put 1 mL of dichloromethane, 0.054 mmol of phenyl boron dichloride, 0.27 mmol of α-isopropyl propenal and 0.405 mmol of α-phenyl styrene into a reaction container, and react at -20°C for 6 h;

[0324] (2) Add 0.15 mmol of triethylamine to the reaction system to quench the reaction, to obtain a reaction mixture;

[0325] (3) Let the reaction mixture stand to room temperature, remove low-boiling substances under reduced pressure, and then purify by column chromatography to obtain a purified 3,4-dihydropyrane derivative.

[0326] The 3,4-dihydropyrane derivative prepared in the embodiment has a structural formula as shown in the following formula (I): The mass is 56.3 mg, and the yield is 75%. The characterization data of the 3,4-dihydropyrane derivative are as follows:

[0327] TLC:R f 0.7(ethyl acetate / hexane=1:20)[KMnO4,UV];

[0328] 1 H NMR (500MHz, CDCl3) δ7.39(d,J=7.9Hz,4H),7.28(t,J=7.6Hz,4H),7.21(q,J=8.1,7.1Hz,2H),6. 44(s,1H),2.49(t,J=6.4Hz,2H),2.14–2.06(m,1H),1.81(t,J=6.3Hz,2H),0.87(d,J=6.8Hz,6H);

[0329] 13 C NMR (126MHz, CDCl3) δ145.23,136.42,128.20,126.98,126.15,118.67,80.58,32.10,31.19,21.56,19.25;

[0330] IR(neat)3061,2963,2928,1667,1500,1453,1175,1114,751,702cm -1 ;

[0331] HRMS(ESI)exact mass calcd.for C 20 H 22 O:m / z 301.1563([M+Na] + ),found:m / z301.1564([M+Na] + ).

[0332] Example 23

[0333] Unactivated acrolein is α-isopropyl acrolein, weakly polarized olefin 1-phenylcyclohexene, R1 is isopropyl, R2 is H, R3 is phenyl, and R4 and R5 are -CH2CH2CH2CH2-.

[0334] Arylboron halides are arylboron halides are Ar represents phenyl, and R represents chlorine.

[0335] The preparation method includes the following steps:

[0336] (1) In a reaction vessel, 1 mL of dichloromethane, 0.054 mmol of phenyl boron dichloride, 0.27 mmol of α-isopropyl propyl aldehyde and 0.405 mmol of α-3-methyl-4-fluorostyrene were put in and reacted at -20°C for 6 h;

[0337] (2) 0.15 mmol of triethylamine was added to the reaction system to quench the reaction, and a reaction mixture was obtained;

[0338] (3) The reaction mixture was left to room temperature, low boiling point substances were removed by distillation under reduced pressure, and then purified by column chromatography to obtain a purified 3,4-dihydropyrane derivative.

[0339] The 3,4-dihydropyrane derivative prepared in this example has a structural formula of The mass was 57.4 mg, and the yield was 83%. The characterization data of the 3,4-dihydropyrane derivative are as follows:

[0340] TLC: R f 0.6 (ethyl acetate / hexane = 1:20) [KMnO4, UV];

[0341] 1 H NMR (500 MHz, CDCl3) δ 7.35 (d, J = 7.4 Hz, 2H), 7.29 (t, J = 7.7 Hz, 2H), 7.21-7.18 (m, 1H), 6.28 (d, J = 1.7 Hz, 1H), 2.22-2.18 (m, 1H), 2.09-2.00 (m, 1H), 1.85-1.77 (m, 2H), 1.73-1.37 (m, 8H), 0.83 (dd, J = 27.7, 6.8 Hz, 6H);

[0342] 13 C NMR (126 MHz, CDCl3) δ 146.82, 134.76, 128.10, 126.40, 124.89, 116.53, 78.79, 40.87, 35.74, 31.13, 27.97, 25.90, 25.76, 22.19, 21.93, 21.33;

[0343] IR (neat) 3065, 2935, 2862, 1671, 1450, 1180, 1121, 1044, 757, 703 cm -1 ;

[0344] HRMS (ESI) exact mass calcd. for C 18 H 24 O: m / z 279.1719 ([M+Na]+ ), found: m / z 279.1714 ([M+Na] + ).

[0345] Example 24

[0346] The unactivated propenal is α-isopropyl propenal, the weakly polarized olefin is α-methyl-β-methyl styrene, R1 is isopropyl, R2 is H, R3 is phenyl, R4 is methyl, and R5 is methyl.

[0347] The aryl boron halide is aryl boron halide is Ar is phenyl, and R is chloro.

[0348] The preparation method comprises the following steps:

[0349] (1) putting 1 mL of dichloromethane, 0.108 mmol of phenyl boron dichloride, 0.27 mmol of α-isopropyl propenal and 0.405 mmol of α-methyl-β-methyl styrene into a reaction container, and reacting at 0 °C for 24 h;

[0350] (2) adding 0.3 mmol of triethylamine to the reaction system to quench the reaction, to obtain a reaction mixture;

[0351] (3) placing the reaction mixture to room temperature, removing low-boiling substances under reduced pressure, and then purifying through column chromatography to obtain a purified 3,4-dihydropyrane derivative.

[0352] The 3,4-dihydropyrane derivative prepared in the example has the structural formula The mass is 36.7 mg, the yield is 59%, and the diastereoselectivity is greater than 20:1. The characterization data of the 3,4-dihydropyrane derivative are as follows: TLC: R f 0.7 (ethyl acetate / hexane=1:20) [KMnO4, UV];

[0353] 1 H NMR (500 MHz, CDCl3) δ 7.39-7.37 (m, 2H), 7.33-7.29 (m, 2H), 7.24-7.21 (m, 1H), 6.29 (s, 1H), 2.19-2.09 (m, 2H), 1.81 (ddd, J=16.7, 5.4, 1.4 Hz, 1H), 1.62 (dd, J=16.7, 7.1 Hz, 1H), 1.43 (s, 3H), 0.95 (dd, J=14.9, 6.9 Hz, 6H), 0.88 (d, J=6.9 Hz, 3H);

[0354] 13C NMR (126 MHz, CDCI3) δ 146.50, 135.68, 128.03, 126.78, 125.42, 116.75, 79.94, 35.49, 31.19, 27.67, 21.71, 21.62, 21.16, 16.00;

[0355] IR (neat) 3036, 2967, 2932, 1665, 1451, 1369, 1181, 1163, 1120, 765, 702 cm -1 ;

[0356] HRMS (ESI) exact mass calcd. for C 16 H 22 O: m / z 253.1563 ([M+Na] + ), found: m / z 253.1562 ([M+Na] + ).

[0357] Example 25

[0358] Unactivated propenal is α-isopropylpropenal, weakly polar olefin 2-phenethylpropene, R1 is isopropyl, R2 is H, R3 is phenethyl, R4 is methyl, and R5 is H.

[0359] Aryl boron halide is aryl boron halide is Ar is phenyl, and R is chloro.

[0360] The preparation method comprises the following steps:

[0361] (1) 1 mL of dichloromethane, 0.054 mmol of phenyl boron dichloride, 0.27 mmol of α-isopropylpropenal and 0.405 mmol of 2-phenethylpropene are put into a reaction container, and the reaction is carried out at 0°C for 8 h;

[0362] (2) 0.15 mmol of triethylamine is added to the reaction system to quench the reaction, and a reaction mixture is obtained;

[0363] (3) The reaction mixture is left to room temperature, low-boiling substances are removed by distillation under reduced pressure, and then the purified 3,4-dihydropyrane derivative is obtained by column chromatography purification.

[0364] The structure of the 3,4-dihydropyrane derivative prepared in the embodiment is as follows: The mass is 33.6 mg, and the yield is 51%. The characterization data of the 3,4-dihydropyrane derivative are as follows:

[0365] TLC: R f0.8 (ethyl acetate / hexane = 1 :20) [KMn04, UV];

[0366] 1 H NMR (500 MHz, CDC13) δ 7.29 - 7.24 (m, 2H), 7.20 - 7.16 (m, 3H), 6.16 (s, 1H), 2.69 - 2.65 (m, 2H), 2.22 - 2.14 (m, 1H), 1.97 - 1.94 (m, 2H), 1.89 - 1.83 (m, 1H), 1.78 - 1.69 (m, 2H), 1.66 - 1.61 (m, 1H), 1.23 (s, 3H), 1.00 (d, J = 6.9 Hz, 6H);

[0367] 13 C NMR (126 MHz, CDC13) δ 142.89, 135.84, 128.49, 128.48, 125.81, 116.62, 74.36, 41.37, 31.59, 31.40, 30.13, 23.65, 21.82, 21.69, 18.48;

[0368] IR (neat) 3034, 2967, 2928, 1665, 1455, 1179, 1110, 1051, 734, 700 cm -1 ;

[0369] HRMS (ESI) exact mass calcd. for C 17 H 24 O: m / z 245.1900 ([M+H] + ), found: m / z 245.1896 ([M+H] + ).

[0370] Example 26

[0371] Unactivated propenals are a-isopropyl propenals, weakly polar olefins 2-methylpentenes, R1 is isopropyl, R2 is H, R3 is propyl, R4 is methyl, R5 is H.

[0372] Aryl boron halides are aryl boron halides are Ar is phenyl, R is chloro.

[0373] The method of preparation comprises the following steps:

[0374] (1) Into a reaction vessel was charged 1 mL of dichloromethane, 0.054 mmol of phenyl boron dichloride, 0.27 mmol of a-isopropyl propenals, and 0.405 mmol of 2-methylpentene, and reacted at 0 °C for 20 h;

[0375] (2) The reaction was quenched by adding 0.15 mmol of triethylamine to the reaction system to obtain a reaction mixture;

[0376] (3) The reaction mixture was left to room temperature, and low-boiling substances were removed by distillation under reduced pressure, and then purified by column chromatography to obtain the purified 3,4-dihydropyrane derivative.

[0377] The 3,4-dihydropyrane derivative prepared in this example has the structural formula The mass was 31.0 mg, and the yield was 63%. The characterization data of the 3,4-dihydropyrane derivative are as follows:

[0378] TLC: R f 0.8 (ethyl acetate / hexane = 1:20) [KMnO4, UV];

[0379] 1 H NMR (500 MHz, CDCl3) δ 7.29-7.24 (m, 2H), 7.20-7.16 (m, 3H), 6.16 (s, 1H), 2.69-2.65 (m, 2H), 2.22-2.14 (m, 1H), 1.97-1.94 (m, 2H), 1.89-1.83 (m, 1H), 1.78-1.69 (m, 2H), 1.66-1.61 (m, 1H), 1.23 (s, 3H), 1.00 (d, J = 6.9 Hz, 6H);

[0380] 13 C NMR (126 MHz, CDCl3) δ 142.89, 135.84, 128.49, 128.48, 125.81, 116.62, 74.36, 41.37, 31.59, 31.40, 30.13, 23.65, 21.82, 21.69, 18.48;

[0381] IR (neat) 3034, 2967, 2928, 1665, 1455, 1179, 1110, 1051, 734, 700 cm -1 ;

[0382] HRMS (ESI) exact mass calcd. for C 17 H 24 O: m / z 245.1900 ([M+H] + ), found: m / z 245.1896 ([M+H] + ).

[0383] The above merely describes preferred embodiments of the present application, and therefore cannot limit the scope of the present application, i.e. equivalent changes and modifications made according to the patent scope and content of the present application should still be within the scope of the present application.

Claims

1. A process for the preparation of 3,4-dihydropyran derivatives, characterized by: The reaction formula is as follows: ， wherein, R1 is selected from C1-C5 alkyl, C1-C5 haloalkyl, cycloalkyl and aryl, and R2 is selected from H, C1-C3 alkyl, R3is selected from the group consisting of C1-C7alkyl and C6-C10aryl; 10 substituted phenyl, R4is selected from the group consisting of H, C1-C7alkyl and aryl, and R5is selected from the group consisting of H and C1-C3alkyl; The structural formula of aryl boron halide is: wherein R is halogen and Ar is aryl.

2. The production method according to claim 1, characterized by: The aryl is selected from phenyl, 1-naphthyl or substituted phenyl with an electron-withdrawing group.

3. The production method according to claim 1, wherein: The solvent is selected from dichloromethane, acetonitrile and 1,2-dichloroethane.

4. The production method according to claim 1, wherein: The aryl in the aryl boron halide is selected from phenyl, 1-naphthyl or substituted phenyl with an electron-withdrawing group; and the solvent is selected from dichloromethane, acetonitrile and 1,2-dichloroethane.

5. The production method according to claim 1, wherein: The method comprises the following steps: (1) mixing the solvent, the aryl boron halide, the unactivated propenal and the weakly polar olefin, and then reacting at -20°C to room temperature for 40 min to 4 d; (2) adding triethylamine to the mixture obtained in step (1) to quench the reaction, to obtain a reaction mixture; (3) allowing the reaction mixture obtained in step (2) to stand to room temperature, removing low-boiling substances under reduced pressure, and then purifying by column chromatography to obtain a purified 3,4-dihydropyrane derivative.

6. The production method according to claim 5, characterized by: The molar ratio of the triethylamine to the aryl boron halide is 2-3:

1.

7. The production method according to any one of claims 1 to 6, characterized by: The molar ratio of the unactivated propenal, the weakly polar olefin and the aryl boron halide is 1.0:1.0-3.0:0.05-0.

4.

8. The production method according to claim 7, characterized by: The ratio of the unactivated propenal to the solvent is 1 mol:1-3 L. The aryl is selected from phenyl, 1-naphthyl or substituted phenyl with an electron-withdrawing group. The solvent is selected from dichloromethane, acetonitrile and 1,2-dichloroethane. The aryl in the aryl boron halide is selected from phenyl, 1-naphthyl or substituted phenyl with an electron-withdrawing group; and the solvent is selected from dichloromethane, acetonitrile and 1,2-dichloroethane. The method comprises the following steps: (1) mixing the solvent, the aryl boron halide, the unactivated propenal and the weakly polar olefin, and then reacting at -20°C to room temperature for 40 min to 4 d; (2) adding triethylamine to the mixture obtained in step (1) to quench the reaction, to obtain a reaction mixture; (3) allowing the reaction mixture obtained in step (2) to stand to room temperature, removing low-boiling substances under reduced pressure, and then purifying by column chromatography to obtain a purified 3,4-dihydropyrane derivative. The molar ratio of the triethylamine to the aryl boron halide is 2-3:

1. The molar ratio of the unactivated propenal, the weakly polar olefin and the aryl boron halide is 1.0:1.0-3.0:0.05-0.

4. The ratio of the unactivated propenal to the solvent is 1 mol:1-3 L.

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