Preparation method of 3, 4-dihydropyran derivative

Abstract

The invention discloses a preparation method of a 3, 4-dihydropyran derivative, and the reaction formula is as follows: # imgabs0. According to the invention, unactivated acrolein and weakly polarized olefin which are simple in structure and low in raw material cost are used as starting raw materials, and the unactivated acrolein and the weakly polarized olefin which are relatively low in reaction activity can participate in [4 + 2] cycloaddition to prepare the 3, 4-dihydropyran derivative with relatively high purity. The invention relates to a 1, 4-dihydropyran derivative. The preparation process is simple and convenient to operate, high in yield and excellent in diastereoselectivity, low-cost raw materials can be effectively converted into high-added-value compounds, and an economical and efficient synthesis strategy is provided for related industries.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis, and specifically relates to a method for preparing a 3,4-dihydropyran derivative. Background Art

[0002] Many physiologically active natural products and drug molecules contain 3,4-dihydropyran or tetrahydropyran structural units, which play an important role in organic synthesis. The oxo[4+2] cycloaddition reaction of acrolein with olefins is considered to be one of the most direct and efficient methods for preparing 3,4-dihydropyran structural units. However, due to the weak reactivity between unactivated acrolein and weakly polarized olefins, this reaction has certain limitations in practical applications. In addition, unactivated acrolein is prone to polymerization under the catalysis of strong Lewis acids, which further increases the difficulty of the oxo[4+2] cycloaddition reaction between unactivated acrolein and weakly polarized olefins, making this process difficult to achieve. Summary of the invention

[0003] The present invention aims to overcome the defects of the prior art and provide a method for preparing 3,4-dihydropyran derivatives.

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

[0005] A method for preparing a 3,4-dihydropyran derivative, characterized in that: the reaction formula is as follows:

[0006]

[0007] in,

[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 The phenyl group is substituted, R4 is selected from H, C1-C7 alkyl and aryl, and R5 is selected from H and C1-C3 alkyl, or R4, R5 and the main body of the obtained 3,4-dihydropyran derivative form a condensed ring structure.

[0010] In a preferred embodiment of the present invention, the structural formula of the aryl boron halide is: Among them, R is a halogen and Ar is an aryl group.

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

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

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

[0014] In a preferred embodiment of the present invention, the steps are as follows:

[0015] (1) mixing the solvent, the arylboron halide, the unactivated acrolein and the weakly polar olefin, and reacting them at -20°C to room temperature for 40 minutes to 4 days;

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

[0017] (3) The reaction mixture obtained in step (2) is allowed to stand at room temperature, low-boiling substances are removed by distillation under reduced pressure, and then purified by column chromatography to obtain a purified 3,4-dihydropyran derivative.

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

[0019] In a preferred embodiment of the present invention, the molar ratio of the unactivated acrolein, 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 acrolein to the solvent is 1 mol:1-3L.

[0021] The beneficial effects of the present invention are:

[0022] 1. The present invention adopts unactivated acrolein and weak polar olefins with simple structure and low raw material cost as starting raw materials, which can enable unactivated acrolein and weak polar olefins with relatively weak reaction activity to participate in [4+2] cycloaddition and prepare 3,4-dihydropyran derivatives with high purity; this preparation process is not only simple to operate, but also has high yield and excellent diastereoselectivity, and can effectively convert low-cost raw materials into high-value-added compounds, providing an economical and efficient synthesis strategy for related industries.

[0023] 2. The 3,4-dihydropyran derivatives synthesized by the present invention 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 solution of the present invention is further illustrated and described below through specific implementation methods.

[0025] Example 1

[0026] The unactivated acrolein is α-ethylacrolein, the weakly polarized olefin is α-methylstyrene, R1 is ethyl, R2 is H, R3 is phenyl, R4 is methyl, and R5 is H.

[0027] Aryl boron halides are Ar is phenyl and R is chlorine.

[0028] The preparation method comprises the following steps:

[0029] (1) 1 mL of dichloromethane, 0.054 mmol of phenylboron dichloride, 0.27 mmol of α-ethylacrolein and 0.405 mmol of α-methylstyrene were placed in a reaction vessel and reacted at -20°C overnight;

[0030] (2) adding 0.11 mmol triethylamine to the reaction system to quench the reaction to obtain a reaction mixture;

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

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

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

[0034] 1 H NMR(500MHz, 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=7.5Hz,3H);

[0035] 13 C NMR (126MHz, CDCl3) δ146.27,136.66,128.22,126.62,124.88,113.82,76.84,33.37,29.09,26.03,21.47,13.06;

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

[0037] HRMS(ESI)exact mass calcd.for C 14 H 18 O: m / z 203.1430 ([M+H] + ),found:m / z203.1430([M+H] + ).

[0038] Example 2

[0039] The unactivated acrolein is α-methylacrolein, the weakly polarized olefin is α-methylstyrene, R1 is methyl, R2 is H, R3 is phenyl, R4 is methyl, and R5 is H.

[0040] Aryl boron halides are Ar is phenyl and R is chlorine.

[0041] The preparation method comprises the following steps:

[0042] (1) 1 mL of dichloromethane, 0.054 mmol of phenylboron dichloride, 0.27 mmol of α-methylacrolein and 0.405 mmol of α-methylstyrene were placed in a reaction vessel and reacted at -20°C overnight;

[0043] (2) adding 0.11 mmol triethylamine to the reaction system to quench the reaction to obtain a reaction mixture;

[0044] (3) The reaction mixture is allowed to stand at room temperature, low boiling point substances are removed by distillation under reduced pressure, and then purified by column chromatography to obtain a purified 3,4-dihydropyran derivative.

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

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

[0047] 1H NMR (500MHz, CDCl3) δ7.37–7.35(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 (126MHz, CDCl3) δ146.22,137.08,128.24,126.62,124.86,108.00,76.58,33.15,29.32,23.66,18.40;

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

[0050] HRMS(ESI)exact mass calcd.for C 13 H 16 O: m / z 211.1093 ([M+Na] + ),found:m / z211.1089([M+Na] + ).

[0051] Example 3

[0052] The unactivated acrolein is α-butyl acrolein, the weakly polarized olefin is α-methylstyrene, R1 is butyl, R2 is H, R3 is phenyl, R4 is methyl, and R5 is H.

[0053] Aryl boron halides are Ar is phenyl and R is bromine.

[0054] The preparation method comprises the following steps:

[0055] (1) 1 mL of dichloromethane, 0.054 mmol of phenylboron dibromide, 0.27 mmol of α-butylacrolein, and 0.405 mmol of α-methylstyrene were placed in a reaction vessel and reacted at -20°C for 6 h;

[0056] (2) adding 0.16 mmol of triethylamine to the reaction system to quench the reaction to obtain a reaction mixture;

[0057] (3) The reaction mixture is allowed to stand at room temperature, low boiling point substances are removed by distillation under reduced pressure, and then purified by column chromatography to obtain a purified 3,4-dihydropyran derivative.

[0058] The structural formula of the 3,4-dihydropyran derivative prepared in this example is 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 (500MHz, CDCl3) δ7.37–7.35(m,2H),7.33–7.30(m,2H),7.23–7.20(m,1H),6.29(s,1H),2.20–2.15(m,1H),1.93–1.8 8(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=7.2Hz,3H);

[0061] 13 C NMR (126MHz, CDCl3) δ146.17,137.30,128.20,126.61,124.90,112.17,76.87,33.34,32.55,30.07,29.22,22.09,21.55,14.01;

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

[0063] HRMS(ESI)exact mass calcd.for C 16 H 22 O: m / z 253.1563 ([M+Na] + ),found:m / z253.1565([M+Na] + ).

[0064] Example 4

[0065] The unactivated acrolein is α-benzyl acrolein, the weakly polarized olefin is α-methylstyrene, R1 is benzyl, R2 is H, R3 is phenyl, R4 is methyl, and R5 is H.

[0066] Aryl boron halides are Ar is phenyl and R is chlorine.

[0067] The preparation method comprises the following steps:

[0068] (1) 1 mL of dichloromethane, 0.054 mmol of phenylboron dichloride, 0.27 mmol of α-benzyl acrolein and 0.405 mmol of α-methylstyrene were placed in a reaction vessel and reacted at -20°C for 6 h;

[0069] (2) adding 0.16 mmol of triethylamine to the reaction system to quench the reaction to obtain a reaction mixture;

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

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

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

[0073] 1 H NMR (500MHz, CDCl3) δ7.39–7.37(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. 0Hz,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 (126MHz, CDCl3) δ145.99,140.40,139.05,128.57,128.30,128.26,126.73,125.98,124.94,111.62,77.22,39.29,33.14,29.30,21.41;

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

[0076] HRMS(ESI)exact mass calcd.for C 19 H 20 O: m / z 265.1587 ([M+H] + ),found:m / z265.1586([M+H] + ).

[0077] Example 5

[0078] The unactivated acrolein is α-isopropyl acrolein, the weakly polarized olefin is α-methylstyrene, R1 is isopropyl, R2 is H, R3 is phenyl, R4 is methyl, and R5 is H.

[0079] Aryl boron halides are Ar is phenyl and R is chlorine.

[0080] The preparation method comprises the following steps:

[0081] (1) 1 mL of dichloromethane, 0.054 mmol of phenylboron dichloride, 0.27 mmol of α-isopropylacrolein and 0.405 mmol of α-methylstyrene were placed in a reaction vessel and reacted at -20°C overnight;

[0082] (2) adding 0.11 mmol triethylamine to the reaction system to quench the reaction to obtain a reaction mixture;

[0083] (3) The reaction mixture is allowed to stand at room temperature, low boiling point substances are removed by distillation under reduced pressure, and then purified by column chromatography to obtain a purified 3,4-dihydropyran derivative.

[0084] The structural formula of the 3,4-dihydropyran derivative prepared in this example is The mass is 49.6 mg and the yield is 85%. The characterization data of the 3,4-dihydropyran derivative are as follows:

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

[0086] 1 H NMR (500MHz, CDCl3) δ7.37–7.35(m,2H),7.33–7.30(m,2H),7.24–7.20(m,1H),6.33(s,1H),2.1 7–2.09(m,2H),1.92–1.84(m,2H),1.65–1.59(m,1H),1.49(s,3H),0.91(dd,J=16.2,6.9Hz,6H);

[0087] 13 C NMR (126MHz, CDCl3) δ146.23,136.11,128.17,126.59,124.84,117.83,76.98,33.52,31.29,28.90,21.71,21.53,18.92;

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

[0089] HRMS(ESI)exact mass calcd.for C 15 H 20 O: m / z 239.1406 ([M+Na] + ),found:m / z239.1409([M+Na] + ).

[0090] Example 6

[0091] The unactivated acrolein is α-cyclohexyl acrolein, the weakly polarized olefin is α-methylstyrene, R1 is cyclohexyl, R2 is H, R3 is phenyl, R4 is methyl, and R5 is H.

[0092] Aryl boron halides are Ar is phenyl and R is chlorine.

[0093] The preparation method comprises the following steps:

[0094] (1) 1 mL of dichloromethane, 0.054 mmol of phenylboron dichloride, 0.27 mmol of α-cyclohexyl acrolein and 0.405 mmol of α-methylstyrene were placed in a reaction vessel and reacted at -20°C overnight;

[0095] (2) adding 0.11 mmol triethylamine to the reaction system to quench the reaction to obtain a reaction mixture;

[0096] (3) The reaction mixture is allowed to stand at room temperature, low boiling point substances are removed by distillation under reduced pressure, and then purified by column chromatography to obtain a purified 3,4-dihydropyran derivative.

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

[0098] TLC:R f0.7(ethyl acetate / hexane=1:20)[KMnO4,UV];

[0099] 1 H NMR (500MHz, CDCl3) δ7.36–7.34(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 (126MHz, CDCl3) δ146.20,136.53,128.15,126.57,124.86,117.47,76.99,41.65,33.59,32.22,32.06,28.96,26.77,26.46,19.70;

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

[0102] HRMS(ESI)exact mass calcd.for C 18 H 24 O: m / z 279.1719 ([M+Na] + ),found:m / z279.1722([M+Na] + ).

[0103] Example 7

[0104] The unactivated acrolein is α-methyl-β-methylacrolein, the weakly polarized olefin is α-methylstyrene, R1 is methyl, R2 is methyl, R3 is phenyl, R4 is methyl, and R5 is H.

[0105] Aryl boron halides are Ar is phenyl and R is chlorine.

[0106] The preparation method comprises the following steps:

[0107] (1) 1 mL of dichloromethane, 0.081 mmol of phenylboron dichloride, 0.27 mmol of α-methyl-β-methylacrolein and 0.405 mmol of α-methylstyrene were placed in a reaction vessel and reacted at 0° C. for 3 days;

[0108] (2) adding 0.2 mmol of triethylamine to the reaction system to quench the reaction to obtain a reaction mixture;

[0109] (3) The reaction mixture is allowed to stand at room temperature, low boiling point substances are removed by distillation under reduced pressure, and then purified by column chromatography to obtain a purified 3,4-dihydropyran derivative.

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

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

[0112] 1 H NMR (500MHz, CDCl3) δ7.44–7.42(m,2H),7.34–7.30(m,2H),7.24–7.21(m,1H),6.23(s,1H),2.31–2.23(m,1 H),2.02(dd,J=13.6,6.0Hz,1H),1.63–1.58(m,1H),1.58–1.56(m,3H),1.51(s,3H),0.94(d,J=7.0Hz,3H);

[0113] 13 C NMR (126MHz, CDCl3) δ147.63,136.55,128.23,126.74,124.59,111.21,76.75,44.24,27.96,24.74,18.48,15.74;

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

[0115] HRMS(ESI)exact mass calcd.for C 14 H 18 O: m / z 225.1250 ([M+Na] + ),found:m / z225.1253([M+Na] + ).

[0116] Example 8

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

[0118] Aryl boron halides are Ar is phenyl and R is chlorine.

[0119] The preparation method comprises the following steps:

[0120] (1) 1 mL of acetonitrile, 0.108 mmol of phenylboron dichloride, 0.27 mmol of α-methyl-β-methylacrolein, and 0.405 mmol of α-methylstyrene were placed in a reaction vessel and reacted at -20°C for 18 h;

[0121] (2) adding 0.31 mmol of triethylamine to the reaction system to quench the reaction to obtain a reaction mixture;

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

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

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

[0125] 1 H NMR (500MHz, CDCl3) δ7.49–7.47(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. 5Hz,1H),2.97–2.89(m,1H),2.23(dd,J=13.8,6.2Hz,1H),1.85(dd,J=13.8,9.2Hz,1H),1.63(s,3H),0.82(d,J=6.9Hz,3H); 13 CNMR(126MHz, CDCl3)δ146.85,140.32,139.10,128.40,128.35,126.97,126.68,125.97,124.66,118.39,77.55,43.78,26.02,25.69,19.34;

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

[0127] HRMS(ESI)exact mass calcd.for C 19 H 20 O: m / z 287.1406 ([M+Na] + ),found:m / z287.1409([M+Na] + ).

[0128] Example 9

[0129] The unactivated acrolein is α-phenyl-β-ethyl acrolein, the weakly polarized olefin is α-methylstyrene, R1 is phenyl, R2 is ethyl, R3 is phenyl, R4 is methyl, and R5 is H.

[0130] Aryl boron halides are Ar is phenyl and R is chlorine.

[0131] The preparation method comprises the following steps:

[0132] (1) 1 mL of dichloromethane, 0.108 mmol of phenylboron dichloride, 0.27 mmol of α-cyclohexyl acrolein, and 0.405 mmol of α-methylstyrene were placed in a reaction vessel and reacted at -20°C for 3 days;

[0133] (2) adding 0.3 mmol of triethylamine to the reaction system to quench the reaction to obtain a reaction mixture;

[0134] (3) The reaction mixture is allowed to stand at room temperature, low boiling point substances are removed by distillation under reduced pressure, and then purified by column chromatography to obtain a purified 3,4-dihydropyran derivative.

[0135] The structural formula of the 3,4-dihydropyran derivative prepared in this example is The mass is 42.1 mg and the yield is 56%. The characterization data of the 3,4-dihydropyran derivative are as follows:

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

[0137] 1H NMR (500MHz, CDCl3) δ7.50–7.48(m,2H),7.39–7.36(m,2H),7.32–7.26(m,3H),7.24–7.18(m,3H),6.69(d,J=1.6Hz,1H),2.79–2.73(m,1 H),2.18(dd,J=13.8,6.3Hz,1H),1.88(dd,J=13.8,9.5Hz,1H),1.63(s,3H),1.51–1.46(m,1H),0.99–0.90(m,1H),0.74(t,J=7.4Hz,3H);

[0138] 13 C NMR (126MHz, CDCl3) δ147.09,140.99,139.27,128.41,128.36,126.99,12 6.73,125.96,124.59,117.78,77.60,39.86,32.29,25.38,25.11,10.72;

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

[0140] HRMS(ESI)exact mass calcd.for C 20 H 22 O: m / z 279.1743 ([M+H] + ),found:m / z279.1741([M+H] + ).

[0141] Example 10

[0142] The unactivated acrolein is α-(3-chloro-n-propyl)acrolein, the weakly polarized olefin is α-methylstyrene, R1 is 3-chloro-n-propyl, R2 is H, R3 is phenyl, R4 is methyl, and R5 is H.

[0143] Aryl boron halides are Ar is phenyl and R is chlorine.

[0144] The preparation method comprises the following steps:

[0145] (1) 1 mL of 1,2-dichloroethane, 0.054 mmol of phenylboron dichloride, 0.27 mmol of α-cyclohexyl acrolein, and 0.405 mmol of α-methylstyrene were added to a reaction vessel and reacted at -20°C for 15 h;

[0146] (2) adding 0.11 mmol triethylamine to the reaction system to quench the reaction to obtain a reaction mixture;

[0147] (3) The reaction mixture is allowed to stand at room temperature, low boiling point substances are removed by distillation under reduced pressure, and then purified by column chromatography to obtain a purified 3,4-dihydropyran derivative.

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

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

[0150] 1 H NMR(500MHz,Chloroform-d)δ7.36–7.30(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 (126MHz, Chloroform-d) δ145.7,138.6,128.3,126.8,124.8,110.0,77.2,44.2,33.0,30.4,29.9,29.6,21.4.

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

[0153] HRMS(ESI)exact mass calcd.for C 18 H 24 O: m / z 273.1017 ([M+Na] + ),found:m / z279.11019([M+Na] + ).

[0154] Embodiment 11

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

[0156] Aryl boron halides are Ar is phenyl and R is chlorine.

[0157] The preparation method comprises the following steps:

[0158] (1) 1 mL of dichloromethane, 0.054 mmol of phenylboron dichloride, 0.27 mmol of α-isopropylacrolein, and 0.405 mmol of α-n-propylstyrene were added to a reaction vessel and reacted at -20°C for 4.5 h;

[0159] (2) adding 0.15 mmol of triethylamine to the reaction system to quench the reaction to obtain a reaction mixture;

[0160] (3) The reaction mixture is allowed to stand at room temperature, low boiling point substances are removed by distillation under reduced pressure, and then purified by column chromatography to obtain a purified 3,4-dihydropyran derivative.

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

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

[0163] 1 H NMR(500MHz, CDCl3)δ7.30(d,J=4.2Hz,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=17.7,6.8Hz,6H),0.80(t,J=7.4Hz,3H);

[0164] 13C NMR (126MHz, CDCl3) δ144.59,136.09,127.97,126.38,125.49,118.16,79.48,44.61,32.00,31.28,21.77,21.44,18.69,16.70,14.55;

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

[0166] HRMS(ESI)exact mass calcd.for C 17 H 24 O: m / z 267.1719 ([M+Na] + ),found:m / z267.1717([M+Na] + ).

[0167] Example 12

[0168] The unactivated acrolein is α-isopropyl acrolein, the weakly polarized olefin is α-n-heptylstyrene, R1 is isopropyl, R2 is H, R3 is phenyl, R4 is n-heptyl, and R5 is H.

[0169] Aryl boron halides are Ar is phenyl and R is chlorine.

[0170] The preparation method comprises the following steps:

[0171] (1) 1 mL of dichloromethane, 0.054 mmol of phenylboron dichloride, 0.27 mmol of α-isopropylacrolein and 0.405 mmol of α-n-heptylstyrene were placed in a reaction vessel and reacted at -20°C overnight;

[0172] (2) adding 0.15 mmol of triethylamine to the reaction system to quench the reaction to obtain a reaction mixture;

[0173] (3) The reaction mixture is allowed to stand at room temperature, low boiling point substances are removed by distillation under reduced pressure, and then purified by column chromatography to obtain a purified 3,4-dihydropyran derivative.

[0174] The structural formula of the 3,4-dihydropyran derivative prepared in this example is The mass is 73.0 mg and the yield is 90%. The characterization data of the 3,4-dihydropyran derivative are as follows:

[0175] TLC:R f0.8(ethyl acetate / hexane=1:20)[KMnO4,UV];

[0176] 1 H NMR (500MHz, CDCl3) δ7.32–7.29(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=6.8Hz,3H),0.84(dd,J=15.2,7.1Hz,6H);

[0177] 13 C NMR (126MHz, CDCl3) δ144.66,136.11,127.98,126.37,125.49,118.17,79.48,42. 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)3065,2928,2861,1669,1469,1448,1173,1120,736,702cm -1 ;

[0179] HRMS(ESI)exact mass calcd.for C 21 H 32 O: m / z 323.2345 ([M+Na] + ),found:m / z323.2346([M+Na] + ).

[0180] Example 13

[0181] The unactivated acrolein is α-isopropyl acrolein, the weakly polarized olefin is α-methyl-p-fluorostyrene, R1 is isopropyl, R2 is H, R3 is methyl-p-fluorophenyl, R4 is methyl, and R5 is H.

[0182] Aryl boron halides are Ar is 1-naphthyl and R is chlorine.

[0183] The preparation method comprises the following steps:

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

[0185] (2) adding 0.15 mmol of triethylamine to the reaction system to quench the reaction to obtain a reaction mixture;

[0186] (3) The reaction mixture is allowed to stand at room temperature, low boiling point substances are removed by distillation under reduced pressure, and then purified by column chromatography to obtain a purified 3,4-dihydropyran derivative.

[0187] The structural formula of the 3,4-dihydropyran derivative prepared in this example is The mass is 60.1 mg and the yield is 95%. The characterization data of the 3,4-dihydropyran derivative are as follows:

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

[0189] 1 H NMR (500MHz, CDCl3) δ7.34–7.30(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=15.4,6.9Hz,6H);

[0190] 13 C NMR(126MHz,CDCl3)δ161.69(d,J CF =244.4Hz),141.96(d,J CF =2.5Hz),136.01,126.56(d,J CF =7.6Hz),117.98,114.92(d,J CF =21.4Hz),76.65,33.53,31.28,29.01,21.71,21.51,18.88;

[0191] IR(neat)3069,2965,2928,1669,1516,1455,1232,1161,1116,832,806,726cm -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] Embodiment 14

[0194] The unactivated acrolein is α-isopropyl acrolein, the 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 halides are Ar is 1-naphthyl and R is chlorine.

[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-isopropylacrolein and 0.405 mmol of α-methyl-p-chlorostyrene were placed in a reaction vessel and reacted at -20°C for 5 h;

[0198] (2) adding 0.15 mmol of triethylamine to the reaction system to quench the reaction to obtain a reaction mixture;

[0199] (3) The reaction mixture is allowed to stand at room temperature, low boiling point substances are removed by distillation under reduced pressure, and then purified by column chromatography to obtain a purified 3,4-dihydropyran derivative.

[0200] The structural formula of the 3,4-dihydropyran derivative prepared in this example is The mass is 50.0 mg and the yield is 74%. The characterization data of the 3,4-dihydropyran derivative are as follows:

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

[0202] 1 H NMR(500MHz, CDCl3)δ7.30–7.26(m,4H),6.30(s,1H),2.16–2.08(m,2H),1.9 0–1.85(m,2H),1.63–1.56(m,1H),1.46(s,3H),0.91(dd,J=14.9,6.9Hz,6H);

[0203] 13C NMR (126MHz, CDCl3) δ144.80,135.98,132.35,128.33,126.44,118.05,76.66,33.36,31.27,28.99,21.71,21.50,18.85;

[0204] IR(neat)3079,2959,2930,1665,1491,1275,1167,1118,1095,1010,828,734cm -1 ;HRMS(ESI)exact mass calcd.for C 15 H 19 ClO: m / z 273.1017 ([M+Na] + ),found:m / z273.1017([M+Na] + ).

[0205] Embodiment 14

[0206] The unactivated acrolein is α-isopropyl acrolein, the weakly polarized olefin is α-methyl-p-trifluoromethylstyrene, R1 is isopropyl, R2 is H, R3 is methyl-p-trifluoromethylbenzene, R4 is methyl, and R5 is H.

[0207] Aryl boron halides are Aryl boron halides are Ar is phenyl and R is chlorine.

[0208] The preparation method comprises the following steps:

[0209] (1) 1 mL of dichloromethane, 0.108 mmol of phenylboron dichloride, 0.27 mmol of α-isopropylacrolein and 0.405 mmol of α-methyl-p-trifluoromethylstyrene were placed in a reaction vessel and reacted 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) The reaction mixture is allowed to stand at room temperature, low boiling point substances are removed by distillation under reduced pressure, and then purified by column chromatography to obtain a purified 3,4-dihydropyran derivative.

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

[0213] TLC:R f0.8(ethyl acetate / hexane=1:20)[KMnO4,UV];

[0214] 1 H NMR(500MHz, CDCl3)δ7.57(d,J=8.3Hz,2H),7.47(d,J=8.2Hz,2H),6.33(s,1H),2.18–2.1 0(m,2H),1.95–1.87(m,2H),1.62–1.55(m,1H),1.49(s,3H),0.91(dd,J=16.1,6.9Hz,6H);

[0215] 13 C NMR(126MHz,CDCl3)δ150.32,135.97,129.98(q,J CF =32.8Hz),125.35,125.22(q,J CF =3.8Hz),124.4(q,J CF =273.4Hz),118.19,76.81,33.32,31.26,28.91,21.68,21.48,18.84; IR(neat)3073,2965,2932,1669,1410,1328,1116,1081,840,708cm -1 ;

[0216] HRMS(ESI)exact mass calcd.for C 16 H 19 FO: m / z 285.1461 ([M+H] + ),found:m / z285.1459([M+H] + ).

[0217] Embodiment 15

[0218] The unactivated acrolein is α-isopropyl acrolein, the weakly polarized olefin is p-methoxystyrene, R1 is isopropyl, R2 is H, R3 is p-methoxyphenyl, R4 is H, and R5 is H.

[0219] Aryl boron halides are Aryl boron halides are Ar is 3,5-dimethylphenyl and R is bromine.

[0220] The preparation method comprises the following steps:

[0221] (1) 1 mL of dichloromethane, 0.054 mmol of 3,5-dichlorophenylboron dibromide, 0.27 mmol of α-isopropylacrolein and 0.405 mmol of p-methoxystyrene were placed in a reaction vessel and reacted at 0°C for 5 h;

[0222] (2) adding 0.15 mmol of triethylamine to the reaction system to quench the reaction to obtain a reaction mixture;

[0223] (3) The reaction mixture is allowed to stand at room temperature, low boiling point substances are removed by distillation under reduced pressure, and then purified by column chromatography to obtain a purified 3,4-dihydropyran derivative.

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

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

[0226] 1 H NMR (500MHz, CDCl3) δ7.28(d,J=8.5Hz,2H),6.88(d,J=8.5Hz,2H),6.38(s,1H),4.66(d, J=10.5Hz,1H),3.80(s,3H),2.24–2.17(m,2H),2.05–1.87(m,3H),1.03(t,J=6.8Hz,6H);

[0227] 13 C NMR (126MHz, CDCl3) δ159.21,138.01,134.51,127.37,118.34,113.89,76.63,55.40,31.37,30.27,21.97,21.48,21.43;

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

[0229] HRMS(ESI)exact mass calcd.for C 15 H 20 O2: m / z 233.1536 ([M+H] + ),found:m / z233.1533([M+H] + ).

[0230] Example 16

[0231] The unactivated acrolein is α-isopropyl acrolein, the weakly polarized olefin is 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 halides are Aryl boron halides are Ar is phenyl and R is chlorine.

[0233] The preparation method comprises the following steps:

[0234] (1) 1 mL of dichloromethane, 0.054 mmol of phenylboron dichloride, 0.27 mmol of α-isopropylacrolein and 0.405 mmol of α-methyl-p-methylstyrene were placed in a reaction vessel and reacted at -20°C for 40 minutes;

[0235] (2) adding 0.15 mmol of triethylamine to the reaction system to quench the reaction to obtain a reaction mixture;

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

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

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

[0239] 1 H NMR(500MHz, CDCl3)δ7.25–7.23(m,2H),7.12(d,J=8.0Hz,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=14.7,6.9Hz,6H);

[0240] 13C NMR (126MHz, CDCl3) δ143.34,136.16,136.06,128.87,124.76,117.71,76.89,33.57,31.31,28.90,21.72,21.57,21.12,18.98;

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

[0242] HRMS(ESI)exact mass calcd.for C 16 H 22 O: m / z 253.1563 ([M+Na] + ),found:m / z253.1558([M+Na] + ).

[0243] Embodiment 17

[0244] The unactivated acrolein is α-isopropyl acrolein, the weakly polarized olefin is α-methyl-m-methylstyrene, R1 is isopropyl, R2 is H, R3 is methyl-m-methylphenyl, R4 is methyl, and R5 is H.

[0245] Aryl boron halides are Aryl boron halides are Ar is phenyl and R is chlorine.

[0246] The preparation method comprises the following steps:

[0247] (1) 1 mL of dichloromethane, 0.054 mmol of phenylboron dichloride, 0.27 mmol of α-isopropylacrolein and 0.405 mmol of α-methyl-m-methylstyrene were added to a reaction vessel and reacted 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) The reaction mixture is allowed to stand at room temperature, low boiling point substances are removed by distillation under reduced pressure, and then purified by column chromatography to obtain a purified 3,4-dihydropyran derivative.

[0250] The structural formula of the 3,4-dihydropyran derivative prepared in this example is The mass is 37.9 mg and the yield is 61%. The characterization data of the 3,4-dihydropyran derivative are as follows:

[0251] TLC:R f0.7(ethyl acetate / hexane=1:20)[KMnO4,UV];

[0252] 1 H NMR(500MHz, CDCl3)δ7.22–7.14(m,3H),7.03(d,J=7.3Hz,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=14.5,6.9Hz,6H);

[0253] 13 C NMR (126MHz, CDCl3) δ146.31,137.64,136.14,128.07,127.34,125.53,121.88,117.72,76.93,33.64,31.32,28.58,21.79,21.70,21.61,18.96;

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

[0255] HRMS(ESI)exact mass calcd.for C 16 H 22 O: m / z 231.1743 ([M+H] + ),found:m / z231.1738([M+H] + ).

[0256] Embodiment 18

[0257] The unactivated acrolein is α-isopropyl acrolein, the weakly polarized olefin is α-methyl-o-methylstyrene, R1 is isopropyl, R2 is H, R3 is methyl-o-methylphenyl, R4 is methyl, and R5 is H.

[0258] Aryl boron halides are Aryl boron halides are Ar is phenyl and R is chlorine.

[0259] The preparation method comprises the following steps:

[0260] (1) 1 mL of dichloromethane, 0.054 mmol of phenylboron dichloride, 0.27 mmol of α-isopropylacrolein and 0.405 mmol of α-methyl-o-methylstyrene were placed in a reaction vessel and reacted at 0° C. for 48 h;

[0261] (2) adding 0.15 mmol of triethylamine to the reaction system to quench the reaction to obtain a reaction mixture;

[0262] (3) The reaction mixture is allowed to stand at room temperature, low boiling point substances are removed by distillation under reduced pressure, and then purified by column chromatography to obtain a purified 3,4-dihydropyran derivative.

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

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

[0265] 1 H NMR (500MHz, CDCl3) δ7.38–7.35(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=16.3,6.8Hz,6H);

[0266] 13 C NMR (126MHz, CDCl3) δ143.31,135.61,135.41,132.75,126.95,126.21,125.70,118.03,77.96,32.27,31.27,26.66,22.38,21.67,19.13;

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

[0268] HRMS(ESI)exact mass calcd.for C 16 H 22 O: m / z 231.1743 ([M+H] + ),found:m / z231.1739([M+H] + ).

[0269] Embodiment 18

[0270] The unactivated acrolein is α-isopropyl acrolein, the weakly polarized olefin is 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 halides are Aryl boron halides are Ar is phenyl and R is chlorine.

[0272] The preparation method comprises the following steps:

[0273] (1) 1 mL of dichloromethane, 0.054 mmol of phenylboron dichloride, 0.27 mmol of α-isopropylacrolein and 0.405 mmol of α-methyl-3,5-dimethylstyrene were added to a reaction vessel and reacted at -20°C for 4.5 h;

[0274] (2) adding 0.15 mmol of triethylamine to the reaction system to quench the reaction to obtain a reaction mixture;

[0275] (3) The reaction mixture is allowed to stand at room temperature, low boiling point substances are removed by distillation under reduced pressure, and then purified by column chromatography to obtain a purified 3,4-dihydropyran derivative.

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

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

[0278] 1 H NMR (500MHz, CDCl3) δ6.97(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=13.2,6.9Hz,6H); 13 C NMR (126MHz, CDCl3) δ146.40,137.53,136.13,128.24,122.58,117.59,76.88,33.74,31.33,28.26,21.69,21.67,21.66,18.97;

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

[0280] HRMS(ESI)exact mass calcd.for C 17 H 24 O: m / z 267.1719 ([M+Na] + ),found:m / z267.1715([M+Na] + ).

[0281] Embodiment 19

[0282] The unactivated acrolein is α-isopropyl acrolein, the weakly polarized olefin is 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 halides are Aryl boron halides are Ar is phenyl and R is chlorine.

[0284] The preparation method comprises the following steps:

[0285] (1) 1 mL of dichloromethane, 0.054 mmol of phenylboron dichloride, 0.27 mmol of α-isopropylacrolein, and 0.405 mmol of α-methyl-3,4-dimethylstyrene were placed in a reaction vessel and reacted at -20°C for 4 h;

[0286] (2) adding 0.15 mmol of triethylamine to the reaction system to quench the reaction to obtain a reaction mixture;

[0287] (3) The reaction mixture is allowed to stand at room temperature, low boiling point substances are removed by distillation under reduced pressure, and then purified by column chromatography to obtain a purified 3,4-dihydropyran derivative.

[0288] The structural formula of the 3,4-dihydropyran derivative prepared in this example is The mass is 59.3 mg and the yield is 90%. The characterization data of the 3,4-dihydropyran derivative are as follows:

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

[0290] 1H NMR(500MHz, CDCl3)δ7.12(s,1H),7.09–7.06(m,2H),6.32(s,1H),2.24(d,J=11.5Hz,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=13.7,6.9Hz,6H);

[0291] 13 C NMR (126MHz, CDCl3) δ143.90,136.18,136.16,134.70,129.45,126.06,122. 21,117.57,76.79,33.66,31.32,28.58,21.70,21.65,20.14,19.47,19.00;

[0292] IR(neat)3030,2963,2926,1665,1455,1271,1191,1169,1114,1048,824,736cm -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] Embodiment 20

[0294] The unactivated acrolein is α-isopropyl acrolein, the weakly polarized 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 halides are Aryl boron halides are Ar is phenyl and R is chlorine.

[0296] The preparation method comprises the following steps:

[0297] (1) 1 mL of dichloromethane, 0.054 mmol of phenylboron dichloride, 0.27 mmol of α-isopropylacrolein and 0.405 mmol of α-methyl-1-naphthylethylene were added to a reaction vessel and reacted at -20°C for 5 h;

[0298] (2) adding 0.15 mmol of triethylamine to the reaction system to quench the reaction to obtain a reaction mixture;

[0299] (3) The reaction mixture is allowed to stand at room temperature, low boiling point substances are removed by distillation under reduced pressure, and then purified by column chromatography to obtain a purified 3,4-dihydropyran derivative.

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

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

[0302] 1 H NMR(500MHz, CDCl3)δ7.83–7.79(m,4H),7.49–7.41(m,3H),6.41(s,1H),2.28–2.23(m,1H),2.1 6–2.08(m,1H),1.99–1.87(m,2H),1.67–1.60(m,1H),1.57(s,3H),0.90(dd,J=20.4,6.9Hz,6H);

[0303] 13 C NMR (126MHz, CDCl3) δ143.60,136.14,133.39,132.43,128.25,127.92,127.59,1 25.96,125.66,123.52,117.97,77.12,33.44,31.30,28.91,21.72,21.58,18.99;

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

[0305] HRMS(ESI)exact mass calcd.for C 19 H 22 O: m / z 289.1563 ([M+Na] + ),found:m / z289.1569([M+Na] + ).

[0306] Embodiment 21

[0307] The unactivated acrolein is α-isopropyl acrolein, the weakly polarized olefin is α-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 halides are Aryl boron halides are Ar is phenyl and R is chlorine.

[0309] The preparation method comprises the following steps:

[0310] (1) 1 mL of dichloromethane, 0.054 mmol of phenylboron dichloride, 0.27 mmol of α-isopropylacrolein and 0.405 mmol of α-3-methyl-4-fluorostyrene were placed in a reaction vessel and reacted at -20°C for 5 h;

[0311] (2) adding 0.15 mmol of triethylamine to the reaction system to quench the reaction to obtain a reaction mixture;

[0312] (3) The reaction mixture is allowed to stand at room temperature, low boiling point substances are removed by distillation under reduced pressure, and then purified by column chromatography to obtain a purified 3,4-dihydropyran derivative.

[0313] The structural formula of the 3,4-dihydropyran derivative prepared in this example is The mass is 52.3 mg and the yield is 78%. The characterization data of the 3,4-dihydropyran derivative are as follows:

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

[0315] 1 H NMR(500MHz, CDCl3)δ7.16(dd,J=7.4,2.1Hz,1H),7.14–7.11(m,1H),6.92(t,J=9.0Hz,1H),6.30(s,1H),2.26(d, J=1.7Hz,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=14.4,6.9Hz,6H);

[0316] 13 C NMR(126MHz,CDCl3)δ160.20(d,J CF =243.2Hz),141.71(d,J CF =2.5Hz),136.02,127.99(d,J CF=5.0Hz),124.23(d,J CF =17.6Hz),123.76(d,J CF =7.6Hz),117.83,114.53(d,J CF =21.4Hz),76.58,33.59,31.30,28.74,21.70,21.57,18.90,14.89(d,J CF =2.5Hz);

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

[0318] HRMS(ESI)exact mass calcd.for C 16 H 21 FO: m / z 249.1649 ([M+H] + ),found:m / z249.1649([M+H] + ).

[0319] Embodiment 22

[0320] The unactivated acrolein is α-isopropyl acrolein, the weakly polarized olefin is α-phenylstyrene, R1 is isopropyl, R2 is H, R3 is phenyl, R4 is phenyl, and R5 is H.

[0321] Aryl boron halides are Aryl boron halides are Ar is phenyl and R is chlorine.

[0322] The preparation method comprises the following steps:

[0323] (1) 1 mL of dichloromethane, 0.054 mmol of phenylboron dichloride, 0.27 mmol of α-isopropylacrolein and 0.405 mmol of α-phenylstyrene were added to a reaction vessel and reacted at -20°C for 6 h;

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

[0325] (3) The reaction mixture is allowed to stand at room temperature, low boiling point substances are removed by distillation under reduced pressure, and then purified by column chromatography to obtain a purified 3,4-dihydropyran derivative.

[0326] The structural formula of the 3,4-dihydropyran derivative prepared in this example is The mass is 56.3 mg and the yield is 75%. The characterization data of the 3,4-dihydropyran 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] Embodiment 23

[0333] The unactivated acrolein is α-isopropyl acrolein, the weakly polarized olefin is 1-phenylcyclohexene, R1 is isopropyl, R2 is H, R3 is phenyl, and R4R5 is -CH2CH2CH2CH2-.

[0334] Aryl boron halides are Aryl boron halides are Ar is phenyl and R is chlorine.

[0335] The preparation method comprises the following steps:

[0336] (1) 1 mL of dichloromethane, 0.054 mmol of phenylboron dichloride, 0.27 mmol of α-isopropylacrolein and 0.405 mmol of α-3-methyl-4-fluorostyrene were placed in a reaction vessel and reacted at -20°C for 6 h;

[0337] (2) adding 0.15 mmol of triethylamine to the reaction system to quench the reaction to obtain a reaction mixture;

[0338] (3) The reaction mixture is allowed to stand at room temperature, low boiling point substances are removed by distillation under reduced pressure, and then purified by column chromatography to obtain a purified 3,4-dihydropyran derivative.

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

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

[0341] 1 H NMR(500MHz, CDCl3)δ7.35(d,J=7.4Hz,2H),7.29(t,J=7.7Hz,2H),7.21–7.18(m,1H),6.28(d,J=1.7Hz,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=27.7,6.8Hz,6H);

[0342] 13 C NMR (126MHz, CDCl3) δ146.82,134.76,128.10,126.40,124.89,116.53,78.79,40.87,35.74,31.13,27.97,25.90,25.76,22.19,21.93,21.33;

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

[0344] HRMS(ESI)exact mass calcd.for C 18 H 24 O: m / z 279.1719 ([M+Na]+ ),found:m / z279.1714([M+Na] + ).

[0345] Embodiment 24

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

[0347] Aryl boron halides are Aryl boron halides are Ar is phenyl and R is chlorine.

[0348] The preparation method comprises the following steps:

[0349] (1) 1 mL of dichloromethane, 0.108 mmol of phenylboron dichloride, 0.27 mmol of α-isopropylacrolein, and 0.405 mmol of α-methyl-β-methylstyrene were placed in a reaction vessel and reacted 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) The reaction mixture is allowed to stand at room temperature, low boiling point substances are removed by distillation under reduced pressure, and then purified by column chromatography to obtain a purified 3,4-dihydropyran derivative.

[0352] The structural formula of the 3,4-dihydropyran derivative prepared in this example is 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-dihydropyran derivative are as follows: TLC: R f 0.7(ethyl acetate / hexane=1:20)[KMnO4,UV];

[0353] 1 H NMR (500MHz, CDCl3) δ7.39–7.37(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=16.7,5.4,1.4Hz,1H),1.62(dd,J=16.7,7.1Hz,1H),1.43(s,3H),0.95(dd,J=14.9,6.9Hz,6H),0.88(d,J=6.9Hz,3H);

[0354] 13C NMR (126MHz, CDCl3) δ146.50,135.68,128.03,126.78,125.42,116.75,79.94,35.49,31.19,27.67,21.71,21.62,21.16,16.00;

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

[0356] HRMS(ESI)exact mass calcd.for C 16 H 22 O: m / z 253.1563 ([M+Na] + ),found:m / z253.1562([M+Na] + ).

[0357] Embodiment 25

[0358] The unactivated acrolein is α-isopropyl acrolein, the weakly polarized olefin is 2-phenylethyl acrolein, R1 is isopropyl, R2 is H, R3 is phenylethyl, R4 is methyl, and R5 is H.

[0359] Aryl boron halides are Aryl boron halides are Ar is phenyl and R is chlorine.

[0360] The preparation method comprises the following steps:

[0361] (1) 1 mL of dichloromethane, 0.054 mmol of phenylboron dichloride, 0.27 mmol of α-isopropylacrolein and 0.405 mmol of 2-phenylethylpropene were added to a reaction vessel and reacted at 0°C for 8 h;

[0362] (2) adding 0.15 mmol of triethylamine to the reaction system to quench the reaction to obtain a reaction mixture;

[0363] (3) The reaction mixture is allowed to stand at room temperature, low boiling point substances are removed by distillation under reduced pressure, and then purified by column chromatography to obtain a purified 3,4-dihydropyran derivative.

[0364] The structural formula of the 3,4-dihydropyran derivative prepared in this example is The mass is 33.6 mg and the yield is 51%. The characterization data of the 3,4-dihydropyran derivative are as follows:

[0365] TLC:R f0.8(ethyl acetate / hexane=1:20)[KMnO4,UV];

[0366] 1 H NMR (500MHz, CDCl3) δ7.29–7.24(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=6.9Hz,6H);

[0367] 13 C NMR (126MHz, CDCl3) δ142.89,135.84,128.49,128.48,125.81,116.62,74.36,41.37,31.59,31.40,30.13,23.65,21.82,21.69,18.48;

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

[0369] HRMS(ESI)exact mass calcd.for C 17 H 24 O: m / z 245.1900 ([M+H] + ),found:m / z245.1896([M+H] + ).

[0370] Embodiment 26

[0371] The unactivated acrolein is α-isopropyl acrolein, the weakly polarized olefin is 2-methylpentene, R1 is isopropyl, R2 is H, R3 is propyl, R4 is methyl, and R5 is H.

[0372] Aryl boron halides are Aryl boron halides are Ar is phenyl and R is chlorine.

[0373] The preparation method comprises the following steps:

[0374] (1) 1 mL of dichloromethane, 0.054 mmol of phenylboron dichloride, 0.27 mmol of α-isopropylacrolein and 0.405 mmol of 2-methylpentene were added to a reaction vessel and reacted at 0°C for 20 h;

[0375] (2) adding 0.15 mmol of triethylamine to the reaction system to quench the reaction to obtain a reaction mixture;

[0376] (3) The reaction mixture is allowed to stand at room temperature, low boiling point substances are removed by distillation under reduced pressure, and then purified by column chromatography to obtain a purified 3,4-dihydropyran derivative.

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

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

[0379] 1 H NMR (500MHz, CDCl3) δ7.29–7.24(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=6.9Hz,6H);

[0380] 13 C NMR (126MHz, CDCl3) δ142.89,135.84,128.49,128.48,125.81,116.62,74.36,41.37,31.59,31.40,30.13,23.65,21.82,21.69,18.48;

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

[0382] HRMS(ESI)exact mass calcd.for C 17 H 24 O: m / z 245.1900 ([M+H] + ),found:m / z245.1896([M+H] + ).

[0383] The above description is only a preferred embodiment of the present invention, and therefore cannot be used to limit the scope of the present invention. That is, equivalent changes and modifications made according to the patent scope of the present invention and the contents of the specification should still fall within the scope of the present invention.

Claims

1. A method for preparing a 3,4-dihydropyran derivative, characterized in that: The reaction formula is as follows: in, R1 is selected from C1-C5 alkyl, C1-C5 haloalkyl, cycloalkyl and aryl, R2 is selected from H, C1-C3 alkyl, R3 is selected from C1-C7 alkyl and C6-C 10 The phenyl group is substituted, R4 is selected from H, C1-C7 alkyl and aryl, and R5 is selected from H and C1-C3 alkyl, or R4, R5 and the main body of the obtained 3,4-dihydropyran derivative form a condensed ring structure.

2. The preparation method according to claim 1, characterized in that: The structural formula of the aryl boron halide is: Among them, R is a halogen and Ar is an aryl group.

3. The preparation method according to claim 2, characterized in that: The aryl group is selected from phenyl, 1-naphthyl or a substituted phenyl group having an electron withdrawing group.

4. The preparation method according to claim 1, characterized in that: The solvent is selected from the group consisting of dichloromethane, acetonitrile and 1,2-dichloroethane.

5. The preparation method according to claim 1, characterized in that: The structural formula of the aryl boron halide is: Wherein, R is a halogen, Ar is an aryl group, the aryl group is selected from phenyl, 1-naphthyl or a substituted phenyl group with an electron-withdrawing group; and the solvent is selected from dichloromethane, acetonitrile and 1,2-dichloroethane.

6. The preparation method according to claim 1, characterized in that: The steps include: (1) mixing the solvent, the arylboron halide, the unactivated acrolein and the weakly polar olefin, and reacting them at -20°C to room temperature for 40 minutes to 4 days; (2) adding triethylamine to the material obtained in step (1) to quench the reaction to obtain a reaction mixture; (3) The reaction mixture obtained in step (2) is allowed to stand at room temperature, low-boiling substances are removed by distillation under reduced pressure, and then purified by column chromatography to obtain a purified 3,4-dihydropyran derivative.

7. The preparation method according to claim 6, characterized in that: The molar ratio of the triethylamine to the aryl boron halide is 2 to 3:

1.

8. The preparation method according to any one of claims 1 to 7, characterized in that: The molar ratio of the unactivated acrolein, the weakly polarized olefin and the aryl boron halide is 1.0:1.0-3.0:0.05-0.

4.

9. The preparation method according to claim 8, characterized in that: The ratio of the unactivated acrolein to the solvent is 1 mol:1-3L.

Images