Chiral cis-cyclobutane derivative and method for preparing chiral cis-cyclobutane derivative by taking weakly polarized olefin as substrate

Abstract

The invention discloses a chiral cis-cyclobutane derivative and a method for preparing the chiral cis-cyclobutane derivative by taking weakly polar olefin as a substrate, and the reaction formula is # imgabs0. The chiral cis-cyclobutane derivative can be prepared by taking alpha, beta-unsaturated aldehyde / ketone and weakly polar olefin which are simple in structure and low in raw material cost as raw materials; the preparation method is simple, the yield is high, enantioselectivity and diastereoselectivity are excellent, and the synthesized chiral cis-cyclobutane derivative has potential physiological activity.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis, and particularly relates to a chiral cis-cyclobutane derivative and a method for preparing the same using a weakly polarized olefin as a substrate. Background Art

[0002] Many natural products and drug molecules with physiological activity are alkyl or aryl substituted cyclobutane derivatives, but alkyl or aryl substituted cyclobutane derivatives are difficult to prepare. The [2+2] cycloaddition reaction of α,β-unsaturated aldehydes / ketones with olefins is one of the most direct and efficient methods for preparing chiral cyclobutanes, but currently such reactions face two main challenges: 1) the enantioselectivity in the reaction is difficult to control, resulting in difficulty in product separation, especially the preparation method of chiral cis-cyclobutane, which has not been reported in the literature so far; 2) weakly polarized olefins (such as alkyl olefins and ordinary aryl olefins) are difficult to be used in [2+2] cycloaddition reactions due to their weak reactivity. Summary of the invention

[0003] The purpose of the present invention is to overcome the defects of the prior art and provide a chiral cis-cyclobutane derivative and a method for preparing the same using a weakly polarized olefin as a substrate, which can enable a weakly polarized olefin with relatively weak reaction activity to participate in a [2+2] cycloaddition and prepare a chiral cis-cyclobutane derivative with relatively high purity.

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

[0005] A method for preparing chiral cis-cyclobutane derivatives using weakly polarized olefins as substrates, wherein the reaction formula is:

[0006]

[0007] Wherein, R1 is halogen or C 1～ C6 alkyl, R2 is H, C 1～ C6 alkyl, C 1～ C6 haloalkyl or C 1～ C6 ester group, R3 is H or C 1～ C7 alkyl, R4 is C 1～ C7 alkyl, C 6～ C9 substituted phenyl, R5 is C 1～ C7 alkyl, R6 is H or methyl, or R5, R6 and the main chain form a C 3～ C8 cycloolefin, wherein R1 is preferred over COR3, and R4 is preferred over R5, that is, R1 and R4 are in a cis relationship.

[0008] The molar ratio of α,β-unsaturated aldehyde / ketone, weakly polarized olefin and chiral oxazolidinone cation is 1.0-3.0:1.0:0.05-0.4.

[0009] In some possible implementations, the chiral oxazaborolidine cation is

[0010] At least one of, wherein Ar is at least one of phenyl, 3,5-dimethylphenyl, 2,3-dimethylphenyl, and 2-naphthyl, and R is at least one of 2-methylphenyl, 2-ethylphenyl, 2-methoxyphenyl, 2-ethoxyphenyl, 2-isopropyloxyphenyl, 1-naphthyl and 2-naphthyl.

[0011] In some possible implementations, R1 is halogen, isopropyl or cyclohexane; and / or R2 is H, methyl, ethyl, butyl, methyl propionate, 2-ethylphenyl or 3-bromopropyl; and / or R3 is H, ethyl or n-heptyl.

[0012] In some possible implementations, R4 is methyl, n-propyl, ethyl, phenyl, 4-chlorophenyl, 2-methylphenyl, 4-trifluoromethylphenyl, 3,5-dimethylphenyl, 3-methyl-4-fluorophenyl, 3,4-dimethylphenyl, 3,4,5-trimethoxyphenyl or 3-methylphenyl; R5 is methyl, ethyl, n-propyl or n-heptyl; R6 is H or methyl.

[0013] In some possible implementations, the chiral oxazaborolidine cation is Ar is 2,3-dimethylphenyl, and R is 1-naphthyl or 2-methoxyphenyl.

[0014] In some possible implementations, the feed ratio of α,β-unsaturated aldehyde / ketone and benzene-based solvent is 1 mol: 1-3 L.

[0015] In some possible implementations, the benzene-based solvent is at least one of toluene, m-xylene and trifluoromethyltoluene.

[0016] In some possible implementations, the method further comprises step (2): after the reaction is completed, quenching with triethylamine to obtain a reaction mixture, wherein the molar ratio of the triethylamine to the chiral oxazolidinone cation is 1 to 3:1.

[0017] In some possible implementations, the method further includes step (3): allowing the reaction mixture to stand at room temperature, removing low-boiling substances under reduced pressure, and then purifying the mixture by column chromatography to obtain a purified chiral cis-cyclobutane derivative.

[0018] A chiral cis-cyclobutane derivative is prepared by the above preparation method.

[0019] The present invention has at least the following beneficial effects: the present invention can prepare chiral cis-cyclobutane derivatives using some α,β-unsaturated aldehydes / ketones and weakly polar olefins with simple structures and low raw material costs as raw materials, the preparation method is simple, the yield is high, and the enantioselectivity and diastereoselectivity are excellent, and the synthesized chiral cis-cyclobutane derivatives have potential physiological activity. DETAILED DESCRIPTION

[0020] The technical solution of the present invention is further illustrated and described below through specific implementation methods.

[0021] In the following examples, the water used can be one or more of distilled water, purified water, and drinking water; unless otherwise specified, the detection methods in the following examples are conventional detection methods; the reagents in the following examples are purchased from commercial channels unless otherwise specified.

[0022] Example 1

[0023] The α,β-unsaturated aldehyde / ketone is α-bromoacrolein, the weakly polar olefin is 2-methyl-1-pentene, R1 is Br, R2 is H, R3 is H, R4 is propyl, R5 is methyl, and R6 is H.

[0024] The chiral oxazaboridine cation is Wherein, Ar is 2,3-dimethylphenyl and R is 2-methoxyphenyl.

[0025] The preparation method comprises the following steps:

[0026] (1) 1 mL of toluene, 0.054 mmol of chiral oxazolidinone cation, 0.405 mmol of α,β-unsaturated aldehyde / ketone and 0.27 mmol were placed in a reaction vessel and reacted at 0°C for 0.5 h;

[0027] (2) adding 0.1 mmol of triethylamine to the reaction system to quench the reaction to obtain a reaction mixture;

[0028] (3) The reaction mixture 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 chiral cis-cyclobutane derivative.

[0029] The structure of the chiral cis-cyclobutane derivative obtained is The mass is 27.9 mg, the yield is 47%, and the enantiomeric excess is 98%. The compound is characterized as follows:

[0030] Enantiomeric excess:

[0031] HPLC analysis (Daicel Chiralcel IG, hexane / 2-propanol=99.9:0.1, 0.5mL / min, λ=236nm, t R =13.6min(major)and t R =15.5min(minor).

[0032] R f 0.20(ethyl acetate / hexane=1:100);

[0033] 1 H NMR (500MHz, CDCl3) δ9.50 (s, 1H), 2.99 (m, 1H), 2.27 (m, 1H), 2.02 (td, J = 10.6, 5.4 Hz,1H),1.68(m,2H),1.61(m,1H),1.30(m,2H),1.08(s,3H),0.99(t,J=7.3Hz,3H);

[0034] 13 C NMR (126MHz, CDCl3) δ193.4,73.7,47.6,42.5,29.7,27.4,20.8,17.4,14.6;

[0035] IR(neat)2960,2931,1716,814,760cm -1 ;

[0036] HRMS(ESI)exact mass calcd.for C9H 15 BrO: m / z 219.0379 ([M+H] + ),found:m / z219.0377([M+H] + ); m / z 221.0359 ([M+H] + ),found:m / z 221.0359([M+H] + );

[0037] [α] D 25 =75.833 (c=0.59, CHCl3; 98%ee).

[0038] Example 2

[0039] The α,β-unsaturated aldehyde / ketone is α-bromoacrolein, the weakly polar olefin is 2-ethyl-1-butene, R1 is Br, R2 is H, R3 is H, R4 is ethyl, R5 is ethyl, and R6 is H.

[0040] The chiral oxazaboridine cation is Wherein, Ar is 2,3-dimethylphenyl and R is 2-methoxyphenyl.

[0041] The preparation method comprises the following steps:

[0042] (1) 1 mL of toluene, 0.054 mmol of chiral oxazolidinone cation, 0.405 mmol of α,β-unsaturated aldehyde / ketone and 0.27 mmol were placed in a reaction vessel and reacted at 0°C for 0.5 h;

[0043] (2) adding 0.1 mmol of 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 substances are removed by distillation under reduced pressure, and then purified by column chromatography to obtain a purified chiral cis-cyclobutane derivative.

[0045] The structure of the chiral cis-cyclobutane derivative obtained is The mass is 26.3 mg, the yield is 44%, and the enantiomeric excess is 93%. The compound is characterized as follows:

[0046] Enantiomeric excess:

[0047] HPLC analysis (Daicel Chiralcel OD-H, hexane / 2-propanol=99.9:0.1, 0.3mL / min, λ=254nm, t R =15.6min(minor)and t R =16.1min(major).

[0048] R f 0.20(ethyl acetate / hexane=1:100);

[0049] 1 H NMR(500MHz, CDCl3)δ9.64(s,1H),2.94(ddd,J=12.8,8.9,4.4Hz,1H),2.28–2.22(m,1H),1.96–1.88(m,2 H),1.74–1.67(m,1H),1.63–1.57(m,1H),1.51–1.46(m,2H),0.87(t,J=7.4Hz,3H),0.83(t,J=7.4Hz,3H);

[0050] 13C NMR (126MHz, CDCl3) δ193.5,73.5,51.9,28.4,27.9,27.5,26.2,8.6,7.8;

[0051] IR(neat)2970,2934,1716,834,761cm -1 ;

[0052] HRMS(ESI)exact mass calcd.for C9H 15 BrO: m / z 219.0379 ([M+H] + ),found:m / z219.0380([M+H] + ); m / z 221.0359 ([M+H] + ),found:m / z 221.0357([M+H] + );

[0053] [α] D 25 =39.050 (c=0.89, CHCl3; 93%ee).

[0054] Example 3

[0055] The α,β-unsaturated aldehyde / ketone is α-bromoacrolein, the weakly polar olefin is α-methylstyrene, R1 is Br, R2 is H, R3 is H, R4 is phenyl, R5 is methyl, and R6 is H.

[0056] The chiral oxazaboridine cation is Wherein, Ar is 2,3-dimethylphenyl and R is 2-methoxyphenyl.

[0057] The preparation method comprises the following steps:

[0058] (1) 1 mL of toluene, 0.054 mmol of chiral oxazolidinone cation, 0.405 mmol of α,β-unsaturated aldehyde / ketone and 0.27 mmol were placed in a reaction vessel and reacted at -60°C for 0.5 h;

[0059] (2) adding 0.1 mmol of triethylamine to the reaction system to quench the reaction to obtain a reaction mixture;

[0060] (3) The reaction mixture 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 chiral cis-cyclobutane derivative.

[0061] The structure of the chiral cis-cyclobutane derivative obtained is The mass is 56.3 mg, the yield is 82%, and the enantiomeric excess is 96%. The compound is characterized as follows:

[0062] Enantiomeric excess:

[0063] HPLC analysis (Daicel Chiralcel OJ-H, hexane / 2-propanol=99:1, 1mL / min, λ=236nm,

[0064] t R =9.0min(major)and t R =12.1min(minor).

[0065] R f 0.20(ethyl acetate / hexane=1:100);

[0066] 1 H NMR(500MHz, CDCl3)δ9.67(s,1H),7.40–7.37(m,2H),7.29–7.25(m,1H),7.15–7.13(m,2H),3.28–3.22(m,1H) ),2.94(q,J=9.6Hz,1H),2.19(ddd,J=13.3,9.1,2.8Hz,1H),1.94(ddd,J=10.9,8.5,2.8Hz,1H),1.52(s,3H);

[0067] 13 C NMR (126MHz, CDCl3) δ192.8,146.1,128.3,126.8,126.6,73.5,53.5,28.1,27.5,26.5;

[0068] IR(neat)3025,2965,2950,1715,1495,1445,1375,1290,761cm -1 ;

[0069] HRMS(ESI)exact mass calcd.for C 12 H 13 BrO: m / z 253.0223 ([M+H] + ),found:m / z253.0220([M+H] + ); m / z 277.0022([M+Na] + ),),found:m / z 255.0020([M+Na] + );

[0070] [α] D 25 =48.015 (c=1.04, CHCl3; 96%ee).

[0071] Example 4

[0072] The α,β-unsaturated aldehyde / ketone is α-bromoacrolein, the weakly polar olefin is α-heptylbenzene, R1 is Br, R2 is H, R3 is H, R4 is phenyl, R5 is n-heptyl, and R6 is H.

[0073] The chiral oxazaboridine cation is Wherein, Ar is 2,3-dimethylphenyl and R is 2-methoxyphenyl.

[0074] The preparation method comprises the following steps:

[0075] (1) 1 mL of toluene, 0.054 mmol of chiral oxazolidinone cation, 0.405 mmol of α,β-unsaturated aldehyde / ketone and 0.27 mmol were placed in a reaction vessel and reacted at -40°C for 0.5 h;

[0076] (2) adding 0.1 mmol of triethylamine to the reaction system to quench the reaction to obtain a reaction mixture;

[0077] (3) The reaction mixture 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 chiral cis-cyclobutane derivative.

[0078] The structure of the chiral cis-cyclobutane derivative obtained is The mass is 41.7 mg, the yield is 65%, and the enantiomeric excess is 95%. The compound is characterized as follows:

[0079] Enantiomeric excess:

[0080] HPLC analysis (Daicel Chiralcel OD-H, hexane / 2-propanol=99.9:0.1, 1mL / min, λ=236nm, t R =8.5min(major)and t R =10.4min(minor).

[0081] R f 0.20(ethyl acetate / hexane=1:100);

[0082] 1H NMR(500MHz, CDCl3)δ9.69(s,1H),7.40–7.37(m,2H),7.28–7.27(m,1H),7.11–7.10(m,2H),3.27–3.21(m,1H),2.82(q,J=9.8Hz ,1H),2.17(d,J=25.3Hz,1H),2.01–2.05(m,1H),1.72–1.83(m,2H),1.21–1.11(m,9H),0.82(t,J=7.2Hz,3H),0.64–0.63(m,1H);

[0083] 13 C NMR (126MHz, CDCl3) δ192.9,143.8,128.2,127.4,126.7,74.4,57.8,37.5,31.8,29.9,29.1,27.5,25.3,25.1,22.7,14.2;

[0084] IR(neat)3025,2925,2854,1717,1496,1446,1377,1172,799,761cm -1 ;

[0085] HRMS(ESI)exact mass calcd.for C 17 H 23 BrO: m / z 323.1005 ([M+H] + ),found:m / z323.1001([M+H] + ); m / z 325.0985([M+H] + ),found:m / z 325.0983([M+H] + );

[0086] [α] D 25 =75.439 (c=0.52, CHCl3; 95%ee).

[0087] Example 5

[0088] R1 is Br, R2 is H, R3 is H, R4 is 4-chlorophenyl, R5 is methyl, and R6 is H.

[0089] The chiral oxazaboridine cation is Wherein, Ar is 2,3-dimethylphenyl and R is 2-methoxyphenyl.

[0090] The preparation method comprises the following steps:

[0091] (1) 1 mL of toluene, 0.054 mmol of chiral oxazolidinone cation, 0.405 mmol of α,β-unsaturated aldehyde / ketone and 0.27 mmol were placed in a reaction vessel and reacted at -60°C for 0.5 h;

[0092] (2) adding 0.1 mmol of triethylamine to the reaction system to quench the reaction to obtain a reaction mixture;

[0093] (3) The reaction mixture 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 chiral cis-cyclobutane derivative.

[0094] The structure of the chiral cis-cyclobutane derivative obtained is The mass is 64.9 mg, the yield is 84%, and the enantiomeric excess is 96%. The compound is characterized as follows:

[0095] Enantiomeric excess:

[0096] HPLC analysis (Daicel Chiralcel OJ-H, hexane / 2-propanol=99:1, 1mL / min, λ=236nm, t R =9.1min(major)and t R =11.9min(minor).

[0097] R f 0.20(ethyl acetate / hexane=1:100);

[0098] 1 H NMR (500MHz, CDCl3) δ9.63 (s, 1H), 7.36–7.34 (m, 2H), 7.09–7.07 (m, 2H), 3.23 (dt, J = 13. 4,9.1Hz,1H),2.89(q,J=9.8Hz,1H),2.22–2.16(m,1H),1.96–1.92(m,1H),1.50(s,3H);

[0099] 13 C NMR (126MHz, CDCl3) δ192.6,144.6,132.6,128.5,128.0,72.9,53.0,28.2,27.5,26.4;

[0100] IR(neat)3008,2976,2929,1717,1491,1400,1094,1063,829,761cm -1 ;

[0101] HRMS(ESI)exact mass calcd.for C 12 H 12 BrClO: m / z 286.9833 ([M+H] + ),found:m / z286.9830([M+H] + ); m / z 310.9632([M+Na] + ),found:m / z 310.9631([M+Na] + );

[0102] [α] D 25 =20.302 (c=1.23, CHCl3; 96%ee).

[0103] Example 6

[0104] R1 is Br, R2 is H, R3 is H, R4 is 2-methylphenyl, R5 is methyl, and R6 is H.

[0105] The chiral oxazaboridine cation is Wherein, Ar is 2,3-dimethylphenyl and R is 2-methoxyphenyl.

[0106] The preparation method comprises the following steps:

[0107] (1) 1 mL of toluene, 0.054 mmol of chiral oxazolidinone cation, 0.405 mmol of α,β-unsaturated aldehyde / ketone and 0.27 mmol were placed in a reaction vessel and reacted at -20°C for 0.5 h;

[0108] (2) adding 0.1 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 substances are removed by distillation under reduced pressure, and then purified by column chromatography to obtain a purified chiral cis-cyclobutane derivative.

[0110] The structure of the chiral cis-cyclobutane derivative obtained is The mass is 34.8 mg, the yield is 48%, and the enantiomeric excess is 94%. The compound is characterized as follows:

[0111] Enantiomeric excess:

[0112] HPLC analysis (Daicel Chiralcel OJ-H, hexane / 2-propanol=99:1, 1mL / min, λ=236nm,

[0113] t R =7.1min(major)and t R =9.6min(minor).

[0114] R f 0.20(ethyl acetate / hexane=1:100);

[0115] 1 H NMR(500MHz, CDCl3)δ9.82(s,1H),7.23–7.08(m,3H),7.02–7.00(m,1H),3.29–7.23(m,1H),3.05 (q,J=10.2Hz,1H),2.28(s,3H),2.14(dd,J=13.0,8.8Hz,1H),2.05(t,J=9.3Hz,1H),1.55(s,3H);

[0116] 13 C NMR (126MHz, CDCl3) δ194.4,144.4,134.1,131.7,127.8,126.9,126.0,75.2,55.6,31.2,28.9,24.5,20.4;

[0117] IR(neat)3066,2969,2868,1715,1490,1458,1217,1156,805,760cm -1 ;

[0118] HRMS(ESI)exact mass calcd.for C 13 H 15 BrO: m / z 267.0379 ([M+H] + ),found:m / z267.0377([M+H] + ); m / z 291.0178([M+Na] + ),found:m / z 291.0175([M+Na] + );

[0119] [α] D 25 =70.552 (c=1.18, CHCl3; 94%ee).

[0120] Example 7

[0121] R1 is Br, R2 is H, R3 is H, R4 is 4-trifluoromethylphenyl, R5 is methyl, and R6 is H.

[0122] The chiral oxazaboridine cation is Wherein, Ar is 2,3-dimethylphenyl and R is 2-methoxyphenyl.

[0123] The preparation method comprises the following steps:

[0124] (1) Place 1 mL of toluene, 0.054 mmol of chiral oxazolidinone cation, 0.405 mmol of α,β-unsaturated aldehyde / ketone and 0.27 mmol in a reaction vessel and react at 0°C for 1 h;

[0125] (2) adding 0.1 mmol of triethylamine to the reaction system to quench the reaction to obtain a reaction mixture;

[0126] (3) The reaction mixture 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 chiral cis-cyclobutane derivative.

[0127] The structure of the chiral cis-cyclobutane derivative obtained is The mass is 40.6 mg, the yield is 47%, and the enantiomeric excess is 92%. The compound is characterized as follows:

[0128] Enantiomeric excess:

[0129] HPLC analysis (Daicel Chiralcel OD-H, hexane / 2-propanol=99:1, 1mL / min, λ=236nm, t R =5.9min(minor)and t R =6.7min(major).

[0130] R f 0.20(ethyl acetate / hexane=1:100);

[0131] 1 H NMR(500MHz, CDCl3)δ9.66(s,1H),7.64–7.63(m,2H),7.27–7.25(m,2H),3.29–3.2 3(m,1H),2.94(q,J=9.8Hz,1H),2.24–2.19(m,1H),2.02–1.97(m,1H),1.53(s,3H);

[0132] 13 C NMR(126MHz,CDCl3)δ192.3,150.0,129.0(q,J CF =32.6Hz),127.0,125.4(q,JCF =3.8Hz),124.3(q,J CF =272.4Hz),72.4,53.4,28.1,27.6,26.5;

[0133] IR(neat)3063,2932,2908,1718,1619,1445,1324,1163,838,761cm -1 ;

[0134] HRMS(ESI)exact mass calcd.for C 13 H 12 BrF3O:m / z 321.0096([M+H] + ),found:m / z321.0095([M+H] + ); m / z 323.0076([M+H] + ),found:m / z 323.0075([M+H] + );

[0135] [α] D 25 =77.282 (c=1.63, CHCl3; 92%ee).

[0136] Example 8

[0137] R1 is Br, R2 is H, R3 is H, R4 is 3,5-dimethylphenyl, R5 is methyl, and R6 is H.

[0138] The chiral oxazaboridine cation is Wherein, Ar is 2,3-dimethylphenyl and R is 2-methoxyphenyl.

[0139] The preparation method comprises the following steps:

[0140] (1) 1 mL of toluene, 0.054 mmol of chiral oxazolidinone cation, 0.405 mmol of α,β-unsaturated aldehyde / ketone and 0.27 mmol were placed in a reaction vessel and reacted at -60°C for 0.5 h;

[0141] (2) adding 0.1 mmol of triethylamine to the reaction system to quench the reaction to obtain a reaction mixture;

[0142] (3) The reaction mixture 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 chiral cis-cyclobutane derivative.

[0143] The structure of the chiral cis-cyclobutane derivative obtained is The mass is 61.5 mg, the yield is 81%, and the enantiomeric excess is 98%. The compound is characterized as follows:

[0144] Enantiomeric excess:

[0145] HPLC analysis (Daicel Chiralcel OJ-H, hexane / 2-propanol=99:1, 1mL / min, λ=236nm, t R =4.9min(major)and t R =5.4min(minor).

[0146] R f 0.20(ethyl acetate / hexane=1:100);

[0147] 1 H NMR(500MHz, CDCl3)δ9.67(s,1H),6.90(s,1H),6.72(s,2H),3.26–3.20(m,1H),2.9 1(q,J=9.8Hz,1H),2.34(s,6H),2.19–2.14(m,1H),1.92–1.87(m,1H),1.49(s,3H);

[0148] 13 C NMR (126MHz, CDCl3) δ193.0,146.1,137.7,128.4,124.4,73.7,53.4,28.2,27.4,26.6,21.7;

[0149] IR(neat)3015,2949,2920,1775,1447,1375,1135,1066,849,760cm -1 ;

[0150] HRMS(ESI)exact mass calcd.for C 14 H 17 BrO: m / z 281.0536 ([M+H] + ),found:m / z281.0533([M+H] + ); m / z 305.0335([M+Na] + ),found:m / z 305.0331([M+Na] + );

[0151] [α] D 25=1.816 (c=1.36, CHCl3; 98%ee).

[0152] Example 9

[0153] R1 is Br, R2 is H, R3 is H, R4 is 3-methyl-4-fluorophenyl, R5 is methyl, and R6 is H.

[0154] The chiral oxazaboridine cation is Wherein, Ar is 2,3-dimethylphenyl and R is 2-methoxyphenyl.

[0155] The preparation method comprises the following steps:

[0156] (1) 1 mL of toluene, 0.054 mmol of chiral oxazolidinone cation, 0.405 mmol of α,β-unsaturated aldehyde / ketone and 0.27 mmol were placed in a reaction vessel and reacted at -60°C for 0.5 h;

[0157] (2) adding 0.1 mmol of triethylamine to the reaction system to quench the reaction to obtain a reaction mixture;

[0158] (3) The reaction mixture 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 chiral cis-cyclobutane derivative.

[0159] The structure of the chiral cis-cyclobutane derivative obtained is The mass is 60.5 mg, the yield is 79%, and the enantiomeric excess is 95%. The compound is characterized as follows:

[0160] Enantiomeric excess:

[0161] HPLC analysis (Daicel Chiralcel OD-H, hexane / 2-propanol=99:1, 1mL / min, λ=236nm, t R =5.1min(minor)and t R =5.5min(major).

[0162] R f 0.20(ethyl acetate / hexane=1:100);

[0163] 1H NMR(500MHz, CDCl3)δ9.64(s,1H),7.02–6.98(m,1H),6.93–6.90(m,2H),3.26–3 .19(m,1H),2.89(q,J=9.8Hz,1H),2.30(s,3H),2.21–3.16(m,1H),1.94–1.90(m Hz,1H),1.50(s,3H);

[0164] 13 C NMR (126MHz, CDCl3) δ192.8,161.1(d,J CF =244.7Hz),141.6(d,J CF =3.6Hz),129.6(d,J CF =5.2Hz),125.5(d,J CF =8.1Hz),124.6(d,J CF =17.4Hz),114.8(d,J CF =22.6Hz),73.4,52.9,28.3,27.4,26.6,15.0(d,J CF =3.4Hz);

[0165] IR(neat)3015,2955,2928,1717,1503,1449,1231,1120,820,759cm -1 ;

[0166] HRMS(ESI)exact mass calcd.for C 13 H 14 BrFO: m / z 285.0285 ([M+H] + ),found:m / z285.0283([M+H] + ); m / z 309.0084 ([M+Na] + ),found:m / z 309.0081([M+Na] + );

[0167] [α] D 25 =59.141 (c=0.90, CHCl3; 95%ee).

[0168] Example 10

[0169] R1 is Br, R2 is H, R3 is H, R4 is 3,4-dimethylphenyl, R5 is methyl, and R6 is H.

[0170] The chiral oxazaboridine cation is Wherein, Ar is 2,3-dimethylphenyl and R is 2-methoxyphenyl.

[0171] The preparation method comprises the following steps:

[0172] (1) 1 mL of toluene, 0.054 mmol of chiral oxazolidinone cation, 0.405 mmol of α,β-unsaturated aldehyde / ketone and 0.27 mmol were placed in a reaction vessel and reacted at -78°C for 1 h;

[0173] (2) adding 0.1 mmol of triethylamine to the reaction system to quench the reaction to obtain a reaction mixture;

[0174] (3) The reaction mixture 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 chiral cis-cyclobutane derivative.

[0175] The structure of the chiral cis-cyclobutane derivative obtained is The mass is 55.9 mg, the yield is 74%, and the enantiomeric excess is 96%. The compound is characterized as follows:

[0176] Enantiomeric excess:

[0177] HPLC analysis (Daicel Chiralcel OD-H, hexane / 2-propanol=99.9:0.1, 1mL / min, λ=236nm, t R =9.5min(minor)and t R =10.3min(major).

[0178] R f 0.20(ethyl acetate / hexane=1:100);

[0179] 1 H NMR(500MHz, CDCl3)δ9.66(s,1H),7.15–7.14(m,1H),6.89–6.87(m,2H),3.26–3.20(m,1H),2.92(q,J=9 .8Hz,1H),2.29(s,3H),2.27(s,3H),2.18(ddd,J=12.3,9.1,2.6Hz,1H),1.93–1.88(m,1H),1.49(s,3H);

[0180] 13C NMR (126MHz, CDCl3) δ193.0,143.6,136.5,135.1,129.6,127.8,124.1,73.8,53.2,28.2,27.4,26.6,20.2,19.6;

[0181] IR(neat)3015,2925,2854,1717,1505,1450,1375,1083,819,764cm -1 ;

[0182] HRMS(ESI)exact mass calcd.for C 14 H 17 BrO: m / z 281.0536 ([M+H] + ),found:m / z281.0535([M+H] + ); m / z 283.0515([M+H] + ),found:m / z 283.0512([M+H] + );

[0183] [α] D 25 =17.945 (c=0.70, CHCl3; 96%ee).

[0184] Embodiment 11

[0185] R1 is Br, R2 is H, R3 is H, R4 is 3,4,5-trimethoxyphenyl, R5 is methyl, and R6 is H.

[0186] The chiral oxazaboridine cation is Wherein, Ar is 2,3-dimethylphenyl and R is 2-methoxyphenyl.

[0187] The preparation method comprises the following steps:

[0188] (1) 1 mL of toluene, 0.054 mmol of chiral oxazolidinone cation, 0.405 mmol of α,β-unsaturated aldehyde / ketone and 0.27 mmol were placed in a reaction vessel and reacted at -95 °C for 1 h;

[0189] (2) adding 0.1 mmol of triethylamine to the reaction system to quench the reaction to obtain a reaction mixture;

[0190] (3) The reaction mixture 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 chiral cis-cyclobutane derivative.

[0191] The structure of the chiral cis-cyclobutane derivative obtained is The mass is 49.4 mg, the yield is 53%, and the enantiomeric excess is 96%. The compound is characterized as follows:

[0192] Enantiomeric excess:

[0193] HPLC analysis (Daicel Chiralcel OD-H, hexane / 2-propanol=95:5, 1mL / min, λ=236nm, t R =10.1min(major)and t R =13.0min(minor).

[0194] R f 0.20(ethyl acetate / hexane=1:5);

[0195] 1 H NMR(500MHz, CDCl3)δ9.66(s,1H),6.35(s,2H),3.90(s,6H),3.88(s,3H),3.26–3.2 0(m,1H),2.91(q,J=9.8Hz,1H),2.25–2.20(m,1H),1.97–1.93(m,1H),1.55(s,3H);

[0196] 13 C NMR (126MHz, CDCl3) δ192.7,153.0,141.9,136.8,104.0,73.3,61.0,56.3,53.7,28.3,27.4,26.6.

[0197] IR(neat)3015,2961,2935,1717,1587,1510,1453,1412,1340,1122,1005,757cm -1 ;

[0198] HRMS(ESI)exact mass calcd.for C 15 H 19 BrO4: m / z 343.0539 ([M+H] + ),found:m / z343.0540([M+H] + ); m / z 367.0338([M+Na] + ),found:m / z 367.0335([M+Na] + );

[0199] [α] D 25 =48.567 (c=1.05, CHCl3; 96%ee).

[0200] Example 12

[0201] R1 is Br, R2 is H, R3 is H, R4 is phenyl, R5 is methyl, and R6 is methyl.

[0202] The chiral oxazaboridine cation is Wherein, Ar is 2,3-dimethylphenyl and R is 2-methoxyphenyl.

[0203] The preparation method comprises the following steps:

[0204] (1) 1 mL of toluene, 0.054 mmol of chiral oxazolidinone cation, 0.405 mmol of α,β-unsaturated aldehyde / ketone and 0.27 mmol were placed in a reaction vessel and reacted at -60°C for 0.5 h;

[0205] (2) adding 0.1 mmol of triethylamine to the reaction system to quench the reaction to obtain a reaction mixture;

[0206] (3) The reaction mixture 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 chiral cis-cyclobutane derivative.

[0207] The structure of the chiral cis-cyclobutane derivative obtained is The mass is 47.8 mg, the yield is 66%, and the enantiomeric excess is 87%. The compound is characterized as follows:

[0208] Enantiomeric excess:

[0209] HPLC analysis (Daicel Chiralcel OJ-H, hexane / 2-propanol=99:1, 1mL / min, λ=236nm, t R =8.4min(major)and t R =11.1min(minor).

[0210] R f 0.20(ethyl acetate / hexane=1:100);

[0211] 1H NMR(500MHz, CDCl3)δ9.65(s,1H),7.39–7.36(m,2H),7.27–7.24(m,1H),7.12–7.10(m,2H),3.40–3.32( m,1H),2.81(dd,J=13.1,10.8Hz,1H),2.28(dd,J=13.1,8.3Hz,1H),1.37(s,3H),1.21(d,J=6.9Hz,3H);

[0212] 13 C NMR (126MHz, CDCl3) δ192.8,147.1,128.4,126.7,126.5,73.0,55.7,35.0,32.0,21.3,14.1;

[0213] IR(neat)3058,2965,2930,1717,1493,1429,1229,1020,835,758cm -1 ;

[0214] HRMS(ESI)exact mass calcd.for C 13 H 15 BrO: m / z 267.0379 ([M+H] + ),found:m / z267.0377([M+H] + ); m / z 291.0178([M+Na] + ),found:m / z 291.0179([M+Na] + );

[0215] [α] D 25 =85.365 (c=1.06, CHCl3; 87%ee).

[0216] Embodiment 13

[0217] R1 is Br, R2 is H, R3 is H, R4 is phenyl, and R5, R6 and the main body of cyclobutane form a bicyclo[4.2.0]octane structure.

[0218] The chiral oxazaboridine cation is Wherein, Ar is 2,3-dimethylphenyl and R is 2-methoxyphenyl.

[0219] The preparation method comprises the following steps:

[0220] (1) 1 mL of toluene, 0.054 mmol of chiral oxazolidinone cation, 0.405 mmol of α,β-unsaturated aldehyde / ketone and 0.27 mmol were placed in a reaction vessel and reacted at -60°C for 1 h;

[0221] (2) adding 0.1 mmol of triethylamine to the reaction system to quench the reaction to obtain a reaction mixture;

[0222] (3) The reaction mixture 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 chiral cis-cyclobutane derivative.

[0223] The structure of the chiral cis-cyclobutane derivative obtained is The mass is 61.3 mg, the yield is 77%, and the enantiomeric excess is 93%. The compound is characterized as follows:

[0224] Enantiomeric excess:

[0225] HPLC analysis (Daicel Chiralcel OD-H, hexane / 2-propanol=99:1, 1mL / min, λ=236nm, t R =6.2min(major)and t R =6.8min(minor).

[0226] R f 0.20(ethyl acetate / hexane=1:100);

[0227] 1 H NMR(500MHz, CDCl3)δ9.62(s,1H),7.39–7.35(m,2H),7.27–7.24(m,1H),7.17–7.15(m,2H),3.35–3.30(m,1H),3.09–3.04(m,1 H),2.11(dd,J=12.8,8.3Hz,1H),1.98–1.92(m,2H),1.87–1.84(m,1H),1.75–1.66(m,2H),1.47–1.38(m,2H),0.99–0.92m,1H);

[0228] 13 C NMR (126MHz, CDCl3) δ192.5,146.1,128.2,127.6,126.6,74.2,55.3,34.1,31.6,31.2,24.7,21.6,21.1;

[0229] IR(neat)3026,2932,2858,1716,1495,1446,1177,1158,816,759cm -1 ;

[0230] HRMS(ESI)exact mass calcd.for C 15 H 17 BrO: m / z 293.0536 ([M+H] + ),found:m / z293.0537([M+H] + ); m / z 295.0515([M+H] + ),found:m / z 295.0511([M+H] + );

[0231] [α] D 25 =53.273 (c=1.45, CHCl3; 93%ee).

[0232] Embodiment 14

[0233] R1 is Br, R2 is H, R3 is H, R4 is 3-methylphenyl, R5 is methyl, and R6 is H.

[0234] The chiral oxazaboridine cation is Wherein, Ar is 2,3-dimethylphenyl and R is 2-methoxyphenyl.

[0235] The preparation method comprises the following steps:

[0236] (1) 1 mL of toluene, 0.054 mmol of chiral oxazolidinone cation, 0.405 mmol of α,β-unsaturated aldehyde / ketone and 0.27 mmol were placed in a reaction vessel and reacted at -60°C for 0.5 h;

[0237] (2) adding 0.1 mmol of triethylamine to the reaction system to quench the reaction to obtain a reaction mixture;

[0238] (3) The reaction mixture 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 chiral cis-cyclobutane derivative.

[0239] The structure of the chiral cis-cyclobutane derivative obtained is The mass is 59.2 mg, the yield is 82%, and the enantiomeric excess is 97%. The compound is characterized as follows:

[0240] Enantiomeric excess:

[0241] HPLC analysis(Daicel Chiralcel OJ-H,hexane / 2-propanol=99:1,1mL / min,λ=236nm,

[0242] t R =6.7min(major)and t R =8.4min(minor).

[0243] R f 0.20(ethyl acetate / hexane=1:100);

[0244] 1 H NMR(500MHz,CDCl3)δ9.67(s,1H),7.29–7.25(m,2H),7.09–7.08(m,1H),6.94–6.93(m,2H),3.27–3.21(m,1H),2.93(q,J=9.8Hz,1H),2.38(s,3H),2.20–2.16(m,1H),1.94–1.90(m,1H),1.51(s,3H);

[0245] 13 C NMR(126MHz,CDCl3)δ192.9,146.1,137.9,128.2,127.5,127.2,123.7,73.6,53.5,28.2,27.4,26.6,21.8;

[0246] IR(neat)3020,2953,2925,1717,1449,1377,1216,1135,786,758cm -1 ;

[0247] HRMS(ESI)exact mass calcd.for C 13 H 15 BrO:m / z 267.0379([M+H] + ),found:m / z267.0378([M+H] + );m / z 291.0178([M+Na] + ),found:m / z 291.0179([M+Na] + );

[0248] [α] D 25 =25.303(c=0.63,CHCl3;97%ee).

[0249] Embodiment 15

[0250] R1 is Cl, R2 is H, R3 is H, R4 is phenyl, R5 is methyl, and R6 is H.

[0251] The chiral oxazaboridine cation is Wherein, Ar is 2,3-dimethylphenyl and R is 2-methoxyphenyl.

[0252] The preparation method comprises the following steps:

[0253] (1) 1 mL of toluene, 0.054 mmol of chiral oxazolidinone cation, 0.405 mmol of α,β-unsaturated aldehyde / ketone and 0.27 mmol were placed in a reaction vessel and reacted at -60°C for 0.5 h;

[0254] (2) adding 0.1 mmol of triethylamine to the reaction system to quench the reaction to obtain a reaction mixture;

[0255] (3) The reaction mixture 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 chiral cis-cyclobutane derivative.

[0256] The structure of the chiral cis-cyclobutane derivative obtained is The mass is 45.0 mg, the yield is 80%, and the enantiomeric excess is 95%. The compound is characterized as follows:

[0257] Enantiomeric excess:

[0258] HPLC analysis (Daicel Chiralcel OD-H, hexane / 2-propanol=99:1, 1mL / min, λ=236nm, t R =7.3min(minor)and t R =8.5min(major).

[0259] R f 0.20(ethyl acetate / hexane=1:100);

[0260] 1H NMR(500MHz, CDCl3)δ9.67(s,1H),7.40–7.36(m,2H),7.28–7.24(m,1H),7.14–7.12(m,2H),3.20–3. 13(m,1H),2.90(q,J=9.6Hz,1H),2.05(ddd,J=12.7,9.2,3.1Hz,1H),1.97–1.93(m,1H),1.46(s,3H);

[0261] 13 C NMR (126MHz, CDCl3) δ194.5,144.5,128.4,126.7,126.7,77.6,54.2,27.9,27.0,27.0;

[0262] IR(neat)3026,2965,2929,1723,1496,1446,1377,1174,815,760cm -1 ;

[0263] HRMS(ESI)exact mass calcd.for C 12 H 13 ClO: m / z 209.0728 ([M+H] + ),found:m / z209.0729([M+H] + );

[0264] [α] D 25 =52.805 (c=1.08, CHCl3; 95%ee).

[0265] Example 16

[0266] R1 is I, R2 is H, R3 is H, R4 is phenyl, R5 is methyl, and R6 is H.

[0267] The chiral oxazaboridine cation is Wherein, Ar is 2,3-dimethylphenyl and R is 2-methoxyphenyl.

[0268] The preparation method comprises the following steps:

[0269] (1) 1 mL of toluene, 0.054 mmol of chiral oxazolidinone cation, 0.405 mmol of α,β-unsaturated aldehyde / ketone and 0.27 mmol were placed in a reaction vessel and reacted at -60°C for 0.5 h;

[0270] (2) adding 0.1 mmol of triethylamine to the reaction system to quench the reaction to obtain a reaction mixture;

[0271] (3) The reaction mixture 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 chiral cis-cyclobutane derivative.

[0272] The structure of the chiral cis-cyclobutane derivative obtained is The mass is 56.3 mg, the yield is 82%, and the enantiomeric excess is 96%. The compound is characterized as follows:

[0273] Enantiomeric excess:

[0274] HPLC analysis (Daicel Chiralcel OD-H, hexane / 2-propanol=99:1, 1mL / min, λ=236nm, t R =9.5min(minor)and t R =11.6min(major).

[0275] R f 0.20(ethyl acetate / hexane=1:100),

[0276] 1 H NMR(500MHz, CDCl3)δ9.55(s,1H),7.40–7.37(m,2H),7.29–7.25(m,1H),7.15–7.13(m,2H), 3.26–3.20(m,1H),2.97(q,J=9.9Hz,1H),2.31–2.26(m,1H),1.93–1.89(m,1H),1.61(s,3H).

[0277] 13 C NMR (126MHz, CDCl3) δ192.8,149.2,128.3,126.9,126.4,60.1,53.2,29.4,28.2,24.8.

[0278] IR(neat)3026,2967,2861,1707,1496,1446,1375,1170,793,763cm -1 ;

[0279] HRMS(ESI)exact mass calcd.for C 12 H 13 IO: m / z 301.0084 ([M+H] + ),found:m / z301.0083([M+H]+ );

[0280] [α] D 25 =147.718 (c=1.01, CHCl3; 96%ee).

[0281] Embodiment 17

[0282] R1 is Br, R2 is methyl, R3 is H, R4 is phenyl, R5 is methyl, and R6 is H.

[0283] The chiral oxazaboridine cation is Wherein, Ar is 2,3-dimethylphenyl and R is 1-naphthyl.

[0284] The preparation method comprises the following steps:

[0285] (1) 1 mL of toluene, 0.054 mmol of chiral oxazolidinone cation, 0.405 mmol of α,β-unsaturated aldehyde / ketone and 0.27 mmol were placed in a reaction vessel and reacted at -60°C for 24 h;

[0286] (2) adding 0.1 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 substances are removed by distillation under reduced pressure, and then purified by column chromatography to obtain a purified chiral cis-cyclobutane derivative.

[0288] The structure of the chiral cis-cyclobutane derivative obtained is The mass is 56.0 mg, the yield is 78%, and the enantiomeric excess is 98%. The compound is characterized as follows:

[0289] Enantiomeric excess:

[0290] HPLC analysis (Daicel Chiralcel AD-H, hexane / 2-propanol=99:1, 0.5mL / min, λ=236nm, t R =11.7min(major)and t R =16.5min(minor).

[0291] R f 0.20(ethyl acetate / hexane=1:100);

[0292] 1H NMR(500MHz, CDCl3)δ9.68(s,1H),7.38–7.35(m,2H),7.26–7.23(m,1H),7.10–7.08(m,2H),3. 24–3.17(m,1H),2.37(t,J=10.5Hz,1H),2.08–2.04(m,1H),1.54(s,3H),1.13(d,J=6.6Hz,3H);

[0293] 13 C NMR (126MHz, CDCl3) δ193.2,146.1,128.2,126.9,126.6,82.7,51.3,35.9,29.7,27.5,18.8.

[0294] IR(neat)3022,2964,2929,1715,1446,1442,1277,1217,835,762cm -1 ;

[0295] HRMS(ESI)exact mass calcd.for C 13 H 15 BrO: m / z 267.0379 ([M+H] + ),found:m / z267.0377([M+H] + ); m / z 269.0359 ([M+H] + ),found:m / z 269.0357([M+H] + );

[0296] [α] D 25 =7.721 (c=1.08, CHCl3; 98%ee).

[0297] Embodiment 18

[0298] R1 is Br, R2 is n-butyl, R3 is H, R4 is phenyl, R5 is methyl, and R6 is H.

[0299] The chiral oxazaboridine cation is Wherein, Ar is 2,3-dimethylphenyl and R is 1-naphthyl.

[0300] The preparation method comprises the following steps:

[0301] (1) 1 mL of toluene, 0.054 mmol of chiral oxazolidinone cation, 0.405 mmol of α,β-unsaturated aldehyde / ketone and 0.27 mmol were placed in a reaction vessel and reacted at -60°C for 5 days;

[0302] (2) adding 0.1 mmol of triethylamine to the reaction system to quench the reaction to obtain a reaction mixture;

[0303] (3) The reaction mixture 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 chiral cis-cyclobutane derivative.

[0304] The structure of the chiral cis-cyclobutane derivative obtained is The mass is 66.8 mg, the yield is 80%, and the enantiomeric excess is 98%.

[0305] The compound is characterized as follows:

[0306] Enantiomeric excess: HPLC analysis (Daicel Chiralcel OD-H, hexane / 2-propanol = 99:1, 1 mL / min, λ = 254 nm, t R =5.6min(minor)and t R =7.5min(major).

[0307] R f 0.20(ethyl acetate / hexane=1:80);

[0308] 1 H NMR (500MHz, CDCl3) δ9.70 (s, 1H), 7.36 (m, 2H), 7.24 (m, 1H), 7.08 (m, 2H), 3.05 (m, 1H), 2.37 (t, J = 1 0.5Hz,1H),2.03(m,1H),1.53(s,3H),1.49(m,2H),1.35(m,2H),1.25(m,2H),0.89(t,J=7.3Hz,3H);

[0309] 13 C NMR (126MHz, CDCl3) δ193.5,146.2,128.2,126.9,126.6,82.3,77.2,51.1,34.8,34.7,33.7,29.1,27.6,22.8,14.2;

[0310] IR(neat)3026,2960,2930,1716,1496,1379,1217,1152,761cm -1 ;

[0311] HRMS(ESI)exact mass calcd.for C16 H 21 BrO: m / z 309.0849 ([M+H] + ),found:m / z309.0850([M+H] + ); m / z 333.0648([M+Na] + ),found:m / z 333.0648([M+Na] + );

[0312] [α] D 25 =45.860 (c=1.00, CHCl3; 98%ee).

[0313] Embodiment 19

[0314] R1 is Br, R2 is 3-bromopropyl, R3 is H, R4 is phenyl, R5 is methyl, and R6 is H.

[0315] The chiral oxazaboridine cation is Wherein, Ar is 2,3-dimethylphenyl and R is 1-naphthyl.

[0316] The preparation method comprises the following steps:

[0317] (1) 1 mL of toluene, 0.054 mmol of chiral oxazolidinone cation, 0.405 mmol of α,β-unsaturated aldehyde / ketone and 0.27 mmol were placed in a reaction vessel and reacted at -60°C for 8 days;

[0318] (2) adding 0.1 mmol of triethylamine to the reaction system to quench the reaction to obtain a reaction mixture;

[0319] (3) The reaction mixture 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 chiral cis-cyclobutane derivative.

[0320] The structure of the chiral cis-cyclobutane derivative obtained is The mass is 82.8 mg, the yield is 82%, and the enantiomeric excess is 88%. The compound is characterized as follows:

[0321] Enantiomeric excess:

[0322] HPLC analysis (Daicel Chiralcel OD-H, hexane / 2-propanol=99:1, 1mL / min, λ=236nm, t R =10.1min(minor)and t R =16.5min(major).

[0323] R f 0.20 (ethyl acetate / hexane = 1:50);

[0324] 1 1H NMR (500 MHz, CDCl3) δ 9.70 (s, 1H), 7.38–7.35 (m, 2H), 7.27–7.24 (m, 1H), 7.08–7.06 (m, 2H), 3.47–3.38 (m, 2H), 3.12–3.06 (m, 1H), 2.41 (t, J = 10.6 Hz, 1H), 2.07–2.04 (m, 1H), 1.84–1.77 (m, 2H), 1.75–1.69 (m, 1H), 1.68–1.61 (m, 1H), 1.53 (s, 3H);

[0325] 13 13C NMR (126 MHz, CDCl3) δ 193.2, 145.8, 128.3, 126.8, 126.7, 81.7, 51.0, 34.4, 33.7, 33.6, 32.5, 30.1, 27.4;

[0326] IR (neat) 3025, 2964, 2929, 1714, 1496, 1445, 1289, 1028, 805, 725 cm -1 ;

[0327] HRMS (ESI) exact mass calcd. for C 15 H 18 Br2O: m / z 374.9777 ([M + H] + ), found: m / z 374.9780 ([M + H] + ); m / z 372.9797 ([M + H] + ), found: m / z 372.9797 ([M + H] + ); m / z 376.9756 ([M + H] + ), found: m / z 376.9759 ([M + H] + );

[0328] [α] D 25 = 55.066 (c = 1.44, CHCl3; 88% ee).

[0329] Example 20

[0330] R1 is Br, R2 is methyl propionate, R3 is H, R4 is phenyl, R5 is methyl, and R6 is H.

[0331] The chiral oxazaboridine cation is Wherein, Ar is 2,3-dimethylphenyl and R is 1-naphthyl.

[0332] The preparation method comprises the following steps:

[0333] (1) 1 mL of toluene, 0.054 mmol of chiral oxazolidinone cation, 0.405 mmol of α,β-unsaturated aldehyde / ketone and 0.27 mmol were placed in a reaction vessel and reacted at -60°C for 8 days;

[0334] (2) adding 0.1 mmol of triethylamine to the reaction system to quench the reaction to obtain a reaction mixture;

[0335] (3) The reaction mixture 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 chiral cis-cyclobutane derivative.

[0336] The structure of the chiral cis-cyclobutane derivative obtained is The mass is 71.4 mg, the yield is 78%, and the enantiomeric excess is 93%. The compound is characterized as follows:

[0337] Enantiomeric excess:

[0338] HPLC analysis (Daicel Chiralcel OD-H, hexane / 2-propanol=99:1, 1mL / min, λ=236nm, t R =20.4min(minor)and t R =29.1min(major).

[0339] R f 0.20(ethyl acetate / hexane=1:100);

[0340] 1 H NMR(500MHz, CDCl3)δ9.69(s,1H),7.38–7.35(m,2H),7.26–7.23(m,1H),7.08–7.06(m,2H),3.69(s,3H),3.15–3.08(m ,1H),2.41(t,J=10.6Hz,1H),2.33–2.22(m,2H),2.07–2.04(m,1H),1.95–1.88(m,1H),1.84–1.77(m,1H),1.53(s,3H);

[0341] 13 C NMR (126MHz, CDCl3) δ193.0,173.5,145.8,128.3,126.8,126.7,81.2,51.7,50.9,34.2,33.9,31.4,28.9,27.3;

[0342] IR(neat)3025,2950,2925,1733,1712,1496,1444,1288,1173,805,762cm -1 ;

[0343] HRMS(ESI)exact mass calcd.for C 16 H 19 BrO3: m / z 341.0570 ([M+H] + ),found:m / z341.0569([M+H] + ); m / z 361.0410([M+Na] + ),found:m / z 361.0408([M+Na] + );

[0344] [α] D 25 =80.568 (c=1.46, CHCl3; 93%ee).

[0345] Embodiment 21

[0346] R1 is cyclohexyl, R2 is H, R3 is H, R4 is phenyl, R5 is methyl, and R6 is H.

[0347] The chiral oxazaboridine cation is Wherein, Ar is 2,3-dimethylphenyl and R is 1-naphthyl.

[0348] The preparation method comprises the following steps:

[0349] (1) 1 mL of toluene, 0.054 mmol of chiral oxazolidinone cation, 0.405 mmol of α,β-unsaturated aldehyde / ketone and 0.27 mmol were placed in a reaction vessel and reacted at -60°C for 1 h;

[0350] (2) adding 0.1 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 substances are removed by distillation under reduced pressure, and then purified by column chromatography to obtain a purified chiral cis-cyclobutane derivative.

[0352] The structure of the chiral cis-cyclobutane derivative obtained is The mass is 31.8 mg, the yield is 46%, and the enantiomeric excess is 93%. The compound is characterized as follows:

[0353] Enantiomeric excess:

[0354] HPLC analysis (Daicel Chiralcel OJ-H, hexane / 2-propanol=99:1, 0.5mL / min, λ=236nm, t R =20.5min(minor)and t R =26.5min(major).

[0355] R f 0.20(ethyl acetate / hexane=1:100);

[0356] 1 H NMR(500MHz, CDCl3)δ10.12(s,1H),7.30–7.26(m,2H),7.20–7.16(m,3H),2.74–2.68(m 2H),2.67–2.60(m,1H),2.31–2.25(m,1H),2.23–2.15(m,2H),2.08–2. 02(m,1H),1.68–1.60(m,6H),1.56–1.48(m,2H),1.25(d,J=6.9Hz,3H);

[0357] 13 C NMR (126MHz, CDCl3) δ190.4,162.8,147.5,134.6,128.4,127.1,126.0,40.5,38.3,33.1,29.3,29.0,28.6,26.6,23.5,22.4;

[0358] IR(neat)3026,2967,2927,1661,1493,1451,1284,1161,856,763cm -1 ;

[0359] HRMS(ESI)exact mass calcd.for C 18 H 24 O: m / z 280.1753 ([M+Na] + ),found:m / z280.1751([M+Na] + );

[0360] [α] D 25 =70.067 (c=0.60, CHCl3; 93%ee).

[0361] 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 chiral cis-cyclobutane derivatives using weakly polarized olefins as substrates, characterized in that: The reaction formula is: Wherein, R1 is halogen or C 1～ C6 alkyl, R2 is H, C 1～ C6 alkyl, C 1～ C6 haloalkyl or C 1～ C6 ester group, R3 is H or C 1～ C7 alkyl, R4 is C 1～ C7 alkyl, C 6～ C9 substituted phenyl, R5 is C 1～ C7 alkyl, R6 is H or methyl, or R5, R6 and the main body of the cyclobutane derivative form a condensed ring structure; The molar ratio of the α,β-unsaturated aldehyde / ketone, the weakly polarized olefin and the chiral oxazolidinone cation is 1.0-3.0:1.0:0.05-0.

4.

2. The method according to claim 1, characterized in that The chiral oxazolidinone cation is At least one of, wherein Ar is at least one of phenyl, 3,5-dimethylphenyl, 2,3-dimethylphenyl, and 2-naphthyl, and R is at least one of 2-methylphenyl, 2-ethylphenyl, 2-methoxyphenyl, 2-ethoxyphenyl, 2-isopropyloxyphenyl, 1-naphthyl and 2-naphthyl.

3. The method according to claim 1, characterized in that Said R1 is halogen, isopropyl or cyclohexane; And / or, R2 is H, methyl, ethyl, butyl, methyl propionate, 2-ethylphenyl or 3-bromopropyl; And / or, R3 is H, ethyl or n-heptyl.

4. The method according to claim 1, characterized in that R4 is methyl, n-propyl, ethyl, phenyl, 4-chlorophenyl, 2-methylphenyl, 4-trifluoromethylphenyl, 3,5-dimethylphenyl, 3-methyl-4-fluorophenyl, 3,4-dimethylphenyl, 3,4,5-trimethoxyphenyl or 3-methylphenyl; R5 is methyl, ethyl, n-propyl or n-heptyl; The R6 is H or methyl.

5. The method according to claim 1, characterized in that The chiral oxazolidinone cation is The Ar is 2,3-dimethylphenyl, and the R is 1-naphthyl or 2-methoxyphenyl.

6. The method according to any one of claims 1 to 5, characterized in that: The feed ratio of the α,β-unsaturated aldehyde / ketone to the benzene series solvent is 1 mol: 1 to 3 L.

7. The method according to claim 6, characterized in that The benzene solvent is at least one of toluene, m-xylene and trifluoromethyltoluene.

8. The method according to any one of claims 1 to 5, characterized in that The method further comprises step (2): after the reaction is completed, quenching with triethylamine to obtain a reaction mixture, wherein the molar ratio of the triethylamine to the chiral oxazolidinone cation is 1 to 3:

1.

9. The method according to claim 8, characterized in that The method further comprises step (3): allowing the reaction mixture to stand at room temperature, removing low-boiling substances under reduced pressure, and then purifying by column chromatography to obtain a purified chiral cis-cyclobutane derivative.

10. A chiral cis-cyclobutane derivative, characterized in that: Prepared by the preparation method described in any one of claims 1 to 9.

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