CN112174920A - 一种氮杂环卡宾催化合成包含1,3-烯炔官能团的二氢吡喃酮类化合物的制备方法 - Google Patents
一种氮杂环卡宾催化合成包含1,3-烯炔官能团的二氢吡喃酮类化合物的制备方法 Download PDFInfo
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- -1 dihydropyrone compound Chemical class 0.000 title claims abstract description 51
- 125000000524 functional group Chemical group 0.000 title claims abstract description 10
- 238000002360 preparation method Methods 0.000 title claims description 143
- ADLVDYMTBOSDFE-UHFFFAOYSA-N 5-chloro-6-nitroisoindole-1,3-dione Chemical compound C1=C(Cl)C([N+](=O)[O-])=CC2=C1C(=O)NC2=O ADLVDYMTBOSDFE-UHFFFAOYSA-N 0.000 title abstract description 7
- 230000002194 synthesizing effect Effects 0.000 title description 4
- 239000003054 catalyst Substances 0.000 title description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 51
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims abstract description 28
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical class C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims abstract description 24
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical class C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims abstract description 19
- 229930192474 thiophene Chemical class 0.000 claims abstract description 12
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical class C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 claims abstract description 7
- 125000000217 alkyl group Chemical class 0.000 claims abstract description 6
- 125000001424 substituent group Chemical group 0.000 claims description 103
- 238000000034 method Methods 0.000 claims description 30
- 125000005843 halogen group Chemical group 0.000 claims description 19
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 12
- 238000006243 chemical reaction Methods 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
- 150000001875 compounds Chemical class 0.000 claims description 5
- 230000015572 biosynthetic process Effects 0.000 claims description 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 claims description 2
- 238000003786 synthesis reaction Methods 0.000 claims description 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims 1
- OKIJSNGRQAOIGZ-UHFFFAOYSA-N Butopyronoxyl Chemical class CCCCOC(=O)C1=CC(=O)CC(C)(C)O1 OKIJSNGRQAOIGZ-UHFFFAOYSA-N 0.000 abstract description 3
- 238000006555 catalytic reaction Methods 0.000 abstract description 3
- 239000000758 substrate Substances 0.000 abstract description 3
- 239000000376 reactant Substances 0.000 abstract description 2
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 191
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 138
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 92
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 46
- 238000005160 1H NMR spectroscopy Methods 0.000 description 46
- 238000004128 high performance liquid chromatography Methods 0.000 description 46
- 238000002844 melting Methods 0.000 description 43
- 230000008018 melting Effects 0.000 description 43
- 239000007787 solid Substances 0.000 description 43
- 238000004293 19F NMR spectroscopy Methods 0.000 description 7
- 150000001299 aldehydes Chemical class 0.000 description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 150000001555 benzenes Chemical class 0.000 description 6
- 238000004440 column chromatography Methods 0.000 description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical class O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 238000006845 Michael addition reaction Methods 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- LVZWSLJZHVFIQJ-UHFFFAOYSA-N Cyclopropane Chemical compound C1CC1 LVZWSLJZHVFIQJ-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 238000004704 ultra performance liquid chromatography Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- WQRWNOKNRHCLHV-TWGQIWQCSA-N (z)-2-bromo-3-phenylprop-2-enal Chemical compound O=CC(/Br)=C/C1=CC=CC=C1 WQRWNOKNRHCLHV-TWGQIWQCSA-N 0.000 description 1
- UNEATYXSUBPPKP-UHFFFAOYSA-N 1,3-Diisopropylbenzene Chemical compound CC(C)C1=CC=CC(C(C)C)=C1 UNEATYXSUBPPKP-UHFFFAOYSA-N 0.000 description 1
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 1
- CQCAYWAIRTVXIY-UHFFFAOYSA-N 2-(triphenyl-$l^{5}-phosphanylidene)acetaldehyde Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=CC=O)C1=CC=CC=C1 CQCAYWAIRTVXIY-UHFFFAOYSA-N 0.000 description 1
- 125000002103 4,4'-dimethoxytriphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)(C1=C([H])C([H])=C(OC([H])([H])[H])C([H])=C1[H])C1=C([H])C([H])=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 1
- 229910014265 BrCl Inorganic materials 0.000 description 1
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- 239000000370 acceptor Substances 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
- 238000006352 cycloaddition reaction Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 238000003760 magnetic stirring Methods 0.000 description 1
- AUHZEENZYGFFBQ-UHFFFAOYSA-N mesitylene Substances CC1=CC(C)=CC(C)=C1 AUHZEENZYGFFBQ-UHFFFAOYSA-N 0.000 description 1
- 125000001827 mesitylenyl group Chemical group [H]C1=C(C(*)=C(C([H])=C1C([H])([H])[H])C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical group CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 238000006362 organocatalysis Methods 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- PQDJYEQOELDLCP-UHFFFAOYSA-N trimethylsilane Chemical compound C[SiH](C)C PQDJYEQOELDLCP-UHFFFAOYSA-N 0.000 description 1
- CMSYDJVRTHCWFP-UHFFFAOYSA-N triphenylphosphane;hydrobromide Chemical compound Br.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 CMSYDJVRTHCWFP-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
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Abstract
本发明公开了一种氮杂环卡宾催化合成包含1,3‑烯炔官能团的二氢吡喃酮类化合物，其特征在于：所述的衍生物如通式(1)表示：
其中，R1为苯基、取代苯、萘、呋喃、噻吩或烷基；R2为苯基、取代苯、呋喃或噻吩；R3为苯基、取代苯、噻吩或烷基。具有简单结构单元的反应物分子α，β‑不饱和醛和1,3‑炔烯醛能有效在氮杂环卡宾的催化下，高效的制备了包含1,3‑烯炔官能团的二氢吡喃酮类衍生物，并具有底物普适性好、优异的收率和对映选择性高等优点。
Description
技术领域
本发明涉及一种氮杂环卡宾催化合成包含1,3-烯炔官能团的二氢吡喃酮类化合物的制备方法。
背景技术
近二十年来，N-杂环卡宾(NHC)有机催化得到了蓬勃发展。在NHC有机催化环加成反应中，α，β-不饱和醛是一类常见的结构单元，提供多种有用的反应模式中，如作为Michael受体。值得注意的是，Scheidt课题组在2011年利用NHC 和Lewis酸共催化使α，β-不饱和醛分子同分子的Michael加成形成全碳五元环，在2020年Scheidt课题组利用α，β-不饱和醛，通过同分子的Michael加成形成二氢吡喃内酯。2016年，Berkessel通过非手性的NHC催化分子内的α，β-不饱和醛形成双环二氢吡喃内酯。目前，利用NHC有机催化实现不同的α，β-不饱和醛的分子间的Michael加成还没有报道。
发明内容
本发明的目的是为了设计合成一类结构新颖、底物普适性好和高对映选择性的1,3-烯炔官能团的二氢吡喃酮类化合物。
本发明的技术方案是：一种氮杂环卡宾催化合成包含1,3-烯炔官能团的二氢吡喃酮类化合物，所述的衍生物如通式(1)表示：
其中， R1为苯基、取代苯、萘、呋喃、噻吩或烷基；R2为苯基、取代苯、呋喃或噻吩； R3为苯基、取代苯、噻吩或烷基。
所述的R1中的取代苯的取代基为对位、邻位、间位中的一个或一个以上取代，苯环邻位取代基为卤原子、甲基或甲氧基；或苯环间位取代基为卤原子、甲基或三氟甲基；或苯环对位取代基为卤原子、甲基、氰基或三氟甲氧基。
所述的R2中的取代苯的取代基为对位甲基、甲氧基、卤原子或三氟甲基，或邻位为卤原子；或间位为卤原子。
所述的R3中的取代苯的取代基为对位、邻位、间位中的一个或一个以上取代，苯环对位取代基为卤原子、甲基、甲氧基或三氟甲基，或苯环邻位取代基为甲氧基，或苯环间位取代基为卤原子或甲氧基。
所述的衍生物的制备方法，反应通式及过程如下：反应温度为室温，
所述的
的制备方法：
本发明的有益效果：具有简单结构单元的反应物分子α，β-不饱和醛和1,3- 炔烯醛能有效在氮杂环卡宾的催化下，高效的制备了包含1,3-烯炔官能团的二氢吡喃酮类衍生物，并具有底物普适性好、优异的收率和对映选择性高等优点。
具体实施方式
以下介绍本发明的实施例，介绍46个制备实施例。
1,3-炔烯醛的合成路线
(1)将取代甲醛S1(1.0eq)和(甲酰基亚甲基)三苯基膦(1.1eq)加入到 100mL圆底烧瓶中，然后甲苯(60mL)逐渐升温至120℃，反应8小时。待反应体系降温到室温，直接浓缩，柱层析得S2。
(2)将S2(1.0eq)溶解到二甲基亚砜(50mL)中，然后缓慢的加入三苯基膦氢溴酸盐(2.0eq)，升温至80℃，反应8小时。冷却至室温，直接浓缩，柱层析得α-溴代肉桂醛S3。
(3)将S3(1.0eq)，四三苯基膦钯(0.05eq),碘化亚铜(0.1eq)和取代基炔(1.2eq)和四氢呋喃(30mL)加入带有支链的100mL的反应瓶中，置换氮气3次，加入三乙胺(15mL)室温反应12小时。将反应体系导入水中(50mL)，加入乙酸乙酯(50mL*2)萃取，合并有机相水(50mL)洗两次，有机相干燥，浓缩，柱层析分离得到1,3-炔烯醛2。
制备实施例1
制备一种氮杂环卡宾催化合成包含1,3-烯炔官能团的二氢吡喃酮类衍生物的合成路线(I)：
取代基R1为Ph,R2为Ph，R3为Ph，制备实施方法和条件如下：
分别称取α，β-不饱和醛1(0.15mmol)、1,3-炔烯醛2(0.1mmol)、氮杂环卡宾催化剂A(0.02mmol)和三乙胺(0.05mmol)加到配有磁力搅拌子的4毫升反应瓶中，加入1.0mL呋喃，盖上瓶盖，室温搅拌反应24h。湿法上样，通过柱层析分离，洗脱剂极性石油醚：乙酸乙酯＝20:1得到目标化合物3或4，称量后计算相应的产率，化合物通过熔点仪，旋光仪，核磁共振仪NMR，高分辨质谱仪 HRMS和高/超高效液相色谱仪HPLC/UPLC予以表征。
(3S，4R)-3-苄基-4-苯基-5-(苯基乙炔基)-3,4-二氢-2H-吡喃-2-酮(I1)
白色固体，产率：85％，熔点：144-145℃；
[α]D25 ＝-214.1(c＝1.0,CHCl3).
1H NMR(400MHz,CDCl3)δ7.39-7.33(m,3H),7.32-7.28(m,4H),7.27(dd,J＝ 3.9,3.0Hz,2H),7.26-7.22(m,2H),7.14-7.06(m,4H),7.04(s,1H),3.55(d,J＝7.0 Hz,1H),3.45-3.39(m,1H),3.28(dd,J＝14.7,4.7Hz,1H),2.43(dd,J＝14.7,9.6Hz, 1H).
13C NMR(101MHz,CDCl3)δ168.9,144.7,138.2,136.4,131.4(2C),129.1(2C),129.0(2C),128.7(2C),128.5,128.3(4C),128.2,126.7,122.6,108.8,92.8,83.7,45.1(2C),32.3.
HRMS(ESI,m/z):Mass calcd.for C26H21O2[M+H]+,365.1536；found:365.1531.HPLC analysis:99％e.e.(Chiralcel ID,25℃,IPA/Hexane＝1/99,0.5mL/min,254 nm),Rt(major)＝20.5min,Rt(minor)＝22.3min.
制备实施例2
取代基所述的R1中的取代基为苯环邻位-Cl，制备实施方法和条件同制备实施例1。
白色固体，产率：80％，熔点：86-88℃.
[α]D25 ＝-131.6(c＝1.0,CHCl3).
1H NMR(400MHz,CDCl3)δ7.43-7.30(m,6H),7.30-7.26(m,3H),7.23-7.08(m, 5H),7.02(s,1H),3.63(d,J＝7.1Hz,1H),3.57(dd,J＝13.3,6.9Hz,1H),3.16(dd,J ＝14.3,6.2Hz,1H),2.69(dd,J＝14.3,6.9Hz,1H).
13C NMR(101MHz,CDCl3)δ168.8,144.6,136.7,136.0,134.1,132.2,131.4(2C),129.6,129.2(2C),128.5,128.3(3C),128.2(3C),126.7,122.5,108.5,92.8,83.6,46.1,42.9,31.3.
HRMS(ESI,m/z):Mass calcd.for C26H20O2Cl[M+H]+,399.1146；found:399.1147.HPLC analysis:>99％e.e.(Chiralcel OD-H,25℃,IPA/Hexane＝1/99,0.5mL/min,254nm),Rt(major)＝22.3min,Rt(minor)＝26.9min.
制备实施例3
取代基所述的R1中的取代基为苯环邻位-Br，制备实施方法和条件同制备实施例1。
(3S，4R)-3-(2-溴苄基)-4-苯基-5-(苯基乙炔基)-3,4-二氢-2H-吡喃-2-酮(I3)
[α]D25 ＝-260.7(c＝1.0,CHCl3).
1H NMR(400MHz,CDCl3)δ7.56(dd,J＝7.9,1.1Hz,1H),7.33-7.41(m,5H), 7.31-7.26(m,3H),7.24-7.18(m,3H),7.17-7.07(m,2H),7.02(s,1H),3.67(d,J＝ 7.1Hz,1H),3.57(q,J＝6.7Hz,1H),3.14(dd,J＝14.3,6.5Hz,1H),2.70(dd,J＝ 14.3,6.6Hz,1H).
13C NMR(101MHz,CDCl3)δ168.7,144.6,137.8,136.7,132.9,132.4(2C),131.4,129.2(2C),128.6,128.5,128.3(2C),128.2(3C),127.4,124.6,122.6,108.5,92.9, 83.7,46.3,43.2,33.7.
HRMS(ESI,m/z):Mass calcd.for C26H20O2Br[M+H]+,443.0641；found:443.0641.HPLC analysis:99％e.e.(Chiralcel OD-H,25℃,IPA/Hexane＝1/99,0.7mL/min,254nm),Rt(major)＝18.2min,Rt(minor)＝21.3min.
制备实施例4
取代基所述的R1中的取代基为苯环邻位-Me，制备实施方法和条件同制备实施例1。
(3S，4R)-3-(2-甲基苄基)-4-苯基-5-(苯基乙炔基)-3,4-二氢-2H-吡喃-2-酮(I4)
[α]D25 ＝-231.7(c＝1.0,CHCl3).
1H NMR(400MHz,CDCl3)δ7.39–7.29(m,5H),7.27(s,2H),7.25(s,1H),7.16 (d,J＝2.8Hz,3H),7.12-7.08(m,2H),7.07-7.00(m,2H),3.61(d,J＝7.0Hz,1H), 3.44-3.39(m,1H),3.24(dd,J＝15.1,4.7Hz,1H),2.51(dd,J＝15.1,9.4Hz,1H), 2.12(s,3H).
13C NMR(101MHz,CDCl3)δ168.0,143.5,135.6,135.5,135.2,130.3(2C),129.62,128.1(2C),128.0,127.4,127.3(2C),127.1(2C),127.0,125.7,125.0,121.5,107.7,91.8,82.6,44.1,42.3,28.2,18.4.
HRMS(ESI,m/z):Mass calcd.for C27H23O2[M+H]+,379.1693；found:379.1693.
HPLC analysis:99％e.e.(Chiralcel OD-H,25℃,IPA/Hexane＝1/99,0.5mL/min, 254nm),Rt(major)＝35.8min,Rt(minor)＝48.8min.
制备实施例5
取代基所述的R1中的取代基为苯环邻位-OMe，制备实施方法和条件同制备实施例1。
(3S，4R)-3-(2-甲氧基苄基)-4-苯基-5-(苯基乙炔基)-3,4-二氢-2H-吡喃-2- 酮(I5)
[α]D25 ＝-98.7(c＝0.5,CHCl3).
1H NMR(400MHz,CDCl3)δ7.39-7.29(m,5H),7.29-7.26(m,2H),7.26-7.21(m,2H),7.19-7.09(m,2H),7.00(s,1H),6.93-6.80(m,3H),3.83(s,3H),3.66-3.60(m, 1H),3.52(d,J＝7.1Hz,1H),3.22(dd,J＝14.1,5.0Hz,1H),2.46(dd,J＝14.1,8.7 Hz,1H).
13C NMR(101MHz,CDCl3)δ169.4,157.6,144.6,137.0,131.7,131.3(2C),129.0(2C),128.4,128.3(2C),128.2(2C),128.0,127.9,126.2,122.6,120.2,110.1,108.7,92.6,84.0,55.2,45.5,42.4,28.4.
HRMS(ESI,m/z):Mass calcd.for C27H23O3[M+H]+,395.1642；found:395.1643.
HPLC analysis:99％e.e.(Chiralcel OD-H,25℃,IPA/Hexane＝1/99,0.6mL/min, 254nm),Rt(major)＝15.7min,Rt(minor)＝21.5min.
制备实施例6
取代基所述的R1中的取代基为苯环间-F，制备实施方法和条件同制备实施例1。
(3S，4R)-3-(3-氟苄基)-4-苯基-5-(苯基乙炔基)-3,4-二氢-2H-吡喃-2-酮(I6)
[α]D25 ＝-199.2(c＝1.0,CHCl3).
1H NMR(400MHz,CDCl3)δ7.40-7.30(m,5H),7.29-7.26(m,3H),7.25-7.23(m, 1H),7.10(dd,J＝7.8,1.6Hz,2H),7.04(s,1H),6.95(t,J＝8.4,2.4Hz,1H),6.88(d, J＝7.7Hz,1H),6.81(dd,J＝9.9,1.9Hz,1H),3.55(d,J＝7.0Hz,1H),3.41-3.39(m, 1H),3.24(dd,J＝14.7,5.0Hz,1H),2.44(dd,J＝14.7,9.3Hz,1H).
13C NMR(101MHz,CDCl3)δ168.6,162.9(d,J＝246.1Hz),144.6,140.7(d,J＝7.3Hz),136.3,131.4(2C),130.1(d,J＝8.4Hz),129.1(2C),128.5,128.3(3C),128.2(2C),124.7,124.6,122.5,115.9(d,J＝21.3Hz),113.7(d,J＝20.9Hz),92.9,83.5, 45.3,44.9,32.2.
19F NMR(376MHz,CDCl3)δ-112.9.
HRMS(ESI,m/z):Mass calcd.for C26H20O2F[M+H]+,383.1442；found:383.1440.
UPLC analysis:>99％e.e.(Chiralcel IA-U,25℃,IPA/Hexane＝1/99,0.5mL/min, 254nm),Rt(major)＝2.9min,Rt(minor)＝3.1min.
制备实施例7
取代基所述的R1中的取代基为苯环间-Cl，制备实施方法和条件同制备实施例1。
(3S，4R)-3-(3-氯苄基)-4-苯基-5-(苯基乙炔基)-3,4-二氢-2H-吡喃-2-酮(I7)
[α]D25 ＝-199.2(c＝1.0,CHCl3).
1H NMR(400MHz,CDCl3)δ7.41–7.31(m,5H),7.30-7.27(m,3H),7.25-7.22(m, 2H),7.14-7.07(m,3H),7.04(s,1H),7.01-6.94(m,1H),3.54(d,J＝7.0Hz,1H), 3.39(m,1H),3.22(dd,J＝14.7,5.1Hz,1H),2.42(dd,J＝14.7,9.2Hz,1H).
13C NMR(101MHz,CDCl3)δ168.6,144.6,140.3,136.2,134.4(3C),129.9,129.2(3C),128.5,128.3(3C),128.2(2C),127.3,127.0,122.5,108.6,93.0,83.5,45.4,44.9,32.2.
HRMS(ESI,m/z):Mass calcd.for C26H20O2Cl[M+H]+,399.1146；found:399.1148.
HPLC analysis:>99％e.e.(Chiralcel OD-H,25℃,IPA/Hexane＝1/99,0.5mL/min, 254nm),Rt(minor)＝41.6min,Rt(major)＝45.8min.
制备实施例8
取代基所述的R1中的取代基为苯环间-Me，制备实施方法和条件同制备实施例1。
(3S，4R)-3-(3-甲基苄基)-4-苯基-5-(苯基乙炔基)-3,4-二氢-2H-吡喃-2-酮(I8)
[α]D25 ＝-171.1(c＝1.0,CHCl3).
1H NMR(400MHz,CDCl3)δ7.30-7.28(m,2H),7.26-7.08(m,8H),7.08-6.90(m, 5H),6.82(s,2H),3.47(d,J＝6.4Hz,1H),3.34-3.31(m,1H),3.22-3.10(m,1H), 2.43-2.29(m,1H),2.26(s,3H).
13C NMR(101MHz,CDCl3)δ167.9,143.6,137.2,137.0,135.4,130.3(2C),128.8,128.0(2C),127.5,127.4,127.3(2C),127.2(2C),127.1,126.4,125.0,121.5,107.7,91.7,82.7,44.0,43.9,31.1,20.4.
HRMS(ESI,m/z):Mass calcd.for C27H23O2[M+H]+,379.1693；found:379.1691.
HPLC analysis:>99％e.e.(Chiralcel OD-H,25℃,IPA/Hexane＝1/99,0.5mL/min, 254nm),Rt(minor)＝30.8min,Rt(major)＝32.5min.
制备实施例9
取代基所述的R1中的取代基为苯环间-CF3，制备实施方法和条件同制备实施例1。
(3S，4R)-4-苯基-5-(苯基乙炔基)-3-(3-(三氟甲基)苄基)-3,4-二氢-2H- 吡喃-2-酮(I9)
[α]D25 ＝-131.1(c＝1.0,CHCl3).
1H NMR(400MHz,CDCl3)δ7.52(d,J＝7.7Hz,1H),7.48-7.34(m,4H),7.31(dd, J＝7.4,2.4Hz,4H),7.27(t,J＝2.2Hz,2H),7.26-7.22(m,1H),7.09(dd,J＝7.7,1.7 Hz,2H),7.04(s,1H),3.51(d,J＝7.1Hz,1H),3.44-3.41(m,1H),3.27(dd,J＝14.6, 5.4Hz,1H),2.52(dd,J＝14.6,8.9Hz,1H).
13C NMR(101MHz,CDCl3)δ168.5,144.6,139.2,136.2,132.4,131.4(2C),130.9(d,J＝32.1Hz),129.2(2C),129.1,128.6,128.4,128.3(2C),128.2(2C),126.1(d,J ＝3.8Hz),123.7(d,J＝3.8Hz),122.7,122.5,108.5,93.0,83.5,45.6,44.9,32.5.
19F NMR(376MHz,CDCl3)δ-62.6.
HRMS(ESI,m/z):Mass calcd.for C27H20O2F3[M+H]+,433.1410；found:433.1409.
HPLC analysis:99％e.e.(Chiralcel IA,25℃,IPA/Hexane＝1/99,0.5mL/min,254 nm),Rt(major)＝18.9min,Rt(minor)＝19.5min.
制备实施例10
取代基所述的R1中的取代基为苯环对-Cl，制备实施方法和条件同制备实施例1。
(3S，4R)-3-(4-氯苄基)-4-苯基-5-(苯基乙炔基)-3,4-二氢-2H-吡喃-2-酮(I10)
[α]D25 ＝-300.4(c＝0.5,CHCl3).
1H NMR(400MHz,CDCl3)δ7.39-7.27(m,7H),7.25-7.21(m,3H),7.08(dd,J＝ 7.7,1.6Hz,2H),7.01(d,J＝7.4Hz,3H),3.51(d,J＝7.0Hz,1H),3.39-3.33(m,1H), 3.19(dd,J＝14.7,5.1Hz,1H),2.41(dd,J＝14.7,9.3Hz,1H).
13C NMR(101MHz,CDCl3)δ168.6,144.6,136.6,136.2,132.5,131.4(2C),130.4(2C),129.2(2C),128.8(2C),128.5,128.3(2C),128.2(3C),122.5,108.7,93.0,83.5,45.3,44.9,31.9.
HRMS(ESI,m/z):Mass calcd.for C26H20O2Cl[M+H]+,399.1146；found:399.1147.
HPLC analysis:98％e.e.(Chiralcel OD-H,25℃,IPA/Hexane＝1/99,0.7mL/min, 254nm),Rt(minor)＝22.6min,Rt(major)＝25.8min.
制备实施例11
取代基所述的R1中的取代基为苯环对-Br，制备实施方法和条件同制备实施例1。
(3S，4R)-3-(4-溴苄基)-4-苯基-5-(苯基乙炔基)-3,4-二氢-2H-吡喃-2-酮(I11)
[α]D30 ＝-295.9(c＝1in CHCl3).
1H NMR(400MHz,CDCl3)δ7.43(d,J＝8.3Hz,2H),7.39-7.30(m,5H),7.27(d,J ＝1.7Hz,3H),7.09(dd,J＝7.7,1.6Hz,2H),7.03(s,1H),6.97(d,J＝8.3Hz,2H), 3.52(d,J＝7.0Hz,1H),3.37(m,1H),3.18(dd,J＝14.7,5.1Hz,1H),2.40(dd,J＝ 14.7,9.3Hz,1H).
13C NMR(101MHz,CDCl3)δ168.6,144.6,137.2,136.2,131.7(2C),131.4(2C),130.8(2C),129.2(2C),128.5,128.3(3C),128.2(2C),122.5,120.6,108.6,93.0,83.5,45.3,44.9,31.9.
HRMS(ESI,m/z):Mass calcd.for C26H20O2Br[M+H]+,443.0641；found:443.0641.
HPLC analysis:96％e.e.(Chiralcel OD-H,25℃,IPA/Hexane＝2/98,0.3mL/min, 254nm),Rt(minor)＝57.2min,Rt(major)＝69.1min.
制备实施例12
取代基所述的R1中的取代基为苯环对-CH3，制备实施方法和条件同制备实施例1。
(3S，4R)-3-(4-甲基苄基)-4-苯基-5-(苯基乙炔基)-3,4-二氢-2H-吡喃-2-酮(I12)
[α]D25 ＝-370.5(c＝1.0,CHCl3).
1H NMR(400MHz,CDCl3)δ7.38-7.27(m,5H),7.27-7.22(m,3H),7.15-7.06(m, 4H),7.01(s,1H),6.97(d,J＝8.0Hz,2H),3.54(d,J＝7.0Hz,1H),3.35-3.40(m,1H), 3.22(dd,J＝14.7,4.6Hz,1H),2.41-2.35(m,1H),2.33(s,3H).
13C NMR(101MHz,CDCl3)δ169.0,144.7,136.5,136.3,135.0,131.4(2C),129.3(2C),129.0(2C),128.9(2C),128.5,128.3(2C),128.3(2C),128.1,122.6,108.8,92.8,83.8,45.2,45.0,31.8,21.1.
HRMS(ESI,m/z):Mass calcd.for C27H23O2[M+H]+,379.1693；found:379.1691.
HPLC analysis:99％e.e.(Chiralcel IA,25℃,IPA/Hexane＝1/99,0.5mL/min,254 nm),Rt(major)＝18.5min,Rt(minor)＝20.3min.
制备实施例13
取代基所述的R1中的取代基为苯环对-CN，制备实施方法和条件同制备实施例1。
(3S，4R)-3-(4-异氰基苯基)-4-苯基-5-(苯基乙炔基)-3,4-二氢-2H-吡喃-2- 酮(I13)
[α]D25 ＝-130.9(c＝0.5,CHCl3).
1H NMR(400MHz,CDCl3)δ7.64(d,J＝7.9Hz,1H),7.53-7.47(m,1H),7.43- 7.31(m,7H),7.30-7.26(m,3H),7.22-7.15(m,2H),7.04(s,1H),3.75(d,J＝7.2Hz, 1H),3.54(t,J＝7.5,5.8Hz,1H),3.12(dd,J＝14.5,7.7Hz,1H),2.85(dd,J＝14.5, 5.7Hz,1H).
13C NMR(101MHz,CDCl3)δ168.2,144.6,142.8,136.1,132.9,132.8,131.4(2C),131.3,129.3(2C),128.5,128.4,128.3(2C),128.1(2C),127.4,122.5,117.8,112.5,108.4,93.0,83.4,46.9,44.3,32.4.
HRMS(ESI,m/z):Mass calcd.for C27H20NO2[M+H]+,390.1489；found:390.1491.
HPLC analysis:>99％e.e.(Chiralcel IA,25℃,IPA/Hexane＝6/94,0.5mL/min,254nm),Rt(major)＝17.9min,Rt(minor)＝19.5min.
制备实施例14
取代基所述的R1中的取代基为苯环对-OCF3，制备实施方法和条件同制备实施例1。
(3S，4R)-4-苯基-5-(苯基乙炔基)-3-(4-(三氟甲氧基)苄基)-3,4-二氢-2H- 吡喃-2-酮(I14)
[α]D25 ＝-178.6(c＝1.0,CHCl3).
1H NMR(400MHz,CDCl3)δ7.41-7.29(m,5H),7.28(dd,J＝4.5,1.8Hz,3H), 7.20–7.07(m,6H),7.04(s,1H),3.56(d,J＝7.0Hz,1H),3.41-3.36(m,1H),3.21 (dd,J＝14.7,5.3Hz,1H),2.46(dd,J＝14.7,8.9Hz,1H).
13C NMR(101MHz,CDCl3)δ168.6,148.0,144.6,137.0,136.2,131.4(2C),130.4(2C),129.2(2C),128.6,128.3(3C),128.2(2C),122.5,121.8,121.1,119.2,108.6, 93.0,83.5,45.5,45.0,31.9.
19F NMR(376MHz,CDCl3)δ-57.8.
HRMS(ESI,m/z):Mass calcd.for C27H20O3F3[M+H]+,449.1359；found:449.1352.
HPLC analysis:>99％e.e.(Chiralcel IA,25℃,IPA/Hexane＝1/99,0.7mL/min,254nm),Rt(minor)＝15.8min,Rt(major)＝18.3min.
制备实施例15
取代基所述的R1中的取代基为苯环邻-Br,对-CH3，制备实施方法和条件同制备实施例1。
(3S，4R)-3-(2-溴-4-甲基苄基)-4-苯基-5-(苯基乙炔基)-3,4-二氢-2H-吡喃 -2-酮(I15)
[α]D25 ＝-283.2(c＝1.0,CHCl3).
1H NMR(400MHz,CDCl3)δ7.33-7.26(m,4H),7.25-7.23(m,2H),7.22-7.16(m, 3H),7.15-7.08(m,2H),6.96-6.89(m,3H),3.57(d,J＝7.1Hz,1H),3.47(q,J＝6.8 Hz,1H),3.03(dd,J＝14.3,6.4Hz,1H),2.57(dd,J＝14.3,6.8Hz,1H),2.22(s,3H).
13C NMR(101MHz,CDCl3)δ167.7,143.6,137.6,135.6,133.5,132.3,131.0,130.3(2C),128.1(2C),127.4,127.3(2C),127.2(2C),127.1,127.1,123.3,121.5,107.5, 91.8,82.7,45.0,42.1,32.1,19.6.
HRMS(ESI,m/z):Mass calcd.for C27H22O2[M+H]+,457.0783；found:457.0781.
HPLC analysis:>99％e.e.(Chiralcel OD-H,25℃,IPA/Hexane＝1/99,0.7mL/min, 254nm),Rt(major)＝15.5min,Rt(minor)＝17.5min.
制备实施例16
取代基所述的R1中的取代基为苯环间-Cl,对-Br，制备实施方法和条件同制备实施例1。
(3S，4R)-3-(4-溴-3-氯苄基)-4-苯基-5-(苯基乙炔基)-3,4-二氢-2H-吡喃-2-酮(I16)
[α]D25 ＝-215.1(c＝1.0,CHCl3).
1H NMR(400MHz,CDCl3)δ7.54(d,J＝8.2Hz,1H),7.41-7.30(m,5H),7.27(dd, J＝5.0,1.2Hz,3H),7.18(d,J＝2.0Hz,1H),7.09(dd,J＝7.8,1.6Hz,2H),7.03(s, 1H),6.86(dd,J＝8.2,2.1Hz,1H),3.53(d,J＝7.1Hz,1H),3.38-3.33(m,1H),3.14 (dd,J＝14.7,5.5Hz,1H),2.40(dd,J＝14.7,8.9Hz,1H).
13C NMR(101MHz,CDCl3)δ168.4,144.6,139.2,136.1,134.5,133.8,131.4(2C),131.0,129.3(2C),128.7,128.6,128.4,128.3(2C),128.2(2C),122.5,120.6,108.6,93.1,83.4,45.5,44.7,32.0.
HRMS(ESI,m/z):Mass calcd.for C26H19O2BrCl[M+H]+,447.0251；found:447.0251.
HPLC analysis:98％e.e.(Chiralcel OD-H,25℃,IPA/Hexane＝2/98,0.5mL/min, 254nm),Rt(minor)＝25.3min,Rt(major)＝33.2min.
制备实施例17
取代基所述的R1中的取代基为萘，制备实施方法和条件同制备实施例1。
(3S，4R)-3-(萘-2-基甲基)-4-苯基-5-(苯基乙炔基)-3,4-二氢-2H-吡喃-2-酮(I17)
[α]D25 ＝-269.6(c＝0.5,CHCl3).
1H NMR(400MHz,CDCl3)δ7.93-7.83(m,2H),7.78(d,J＝8.2Hz,1H),7.58-7.45 (m,2H),7.44-7.33(m,4H),7.29-7.26(m,2H),7.25-7.18(m,5H),7.16(d,J＝6.8Hz, 1H),6.98(s,1H),3.89-3.78(m,1H),3.60-3.51(m,2H),2.94-2.84(m,1H).
13C NMR(101MHz,CDCl3)δ169.1,144.4,136.7,134.0,134.0,131.5,131.3(2C),129.2(2C),129.1,128.4,128.4(2C),128.3(2C),128.2,127.7,127.6,126.4,125.8,125.3,123.2,122.5,108.8,92.9,83.6,45.3,43.9,29.3.
HRMS(ESI,m/z):Mass calcd.for C30H23O2[M+H]+,415.1693；found:415.1693.
HPLC analysis:99％e.e.(Chiralcel OD-H,25℃,IPA/Hexane＝2/98 0.5mL/min, 254nm),Rt(minor)＝39.1min,Rt(major)＝45.6min.
制备实施例18
取代基所述的R1中的取代基为呋喃，制备实施方法和条件同制备实施例1。 (3S，4R)-3-(呋喃-2-基甲基)-4-苯基-5-(苯基乙炔基)-3,4-二氢-2H-吡喃-2- 酮(I18)
[α]D25 ＝-106.1(c＝1.0,CHCl3).
1H NMR(400MHz,CDCl3)δ7.32-7.26(m,3H),7.25-7.23(m,3H),7.20-7.17(m, 3H),7.10-7.04(m,2H),7.01(s,1H),6.26(dd,J＝3.1,1.9Hz,1H),5.94(d,J＝3.1 Hz,1H),3.60(d,J＝7.0Hz,1H),3.47-3.42(m,1H),3.13(dd,J＝15.8,4.1Hz,1H), 2.39(dd,J＝15.8,9.9Hz,1H).
13C NMR(101MHz,CDCl3)δ167.2,150.8,143.9,140.6,134.8,130.4(2C),128.0(2C),127.5,127.3(4C),127.2,121.5,109.3,107.5,106.3,91.7,82.6,44.2,41.7,24.1
HRMS(ESI,m/z):Mass calcd.for C24H19O3[M+H]+,355.1329；found:355.1328.
HPLC analysis:>99％e.e.(Chiralcel OD-H,25℃,IPA/Hexane＝2/98,0.7mL/min, 254nm),Rt(major)＝13.0min,Rt(minor)＝14.3min.
制备实施例19
取代基所述的R1中的取代基为噻吩，制备实施方法和条件同制备实施例1。 (3S，4R)-4-苯基-5-(苯基乙炔基)-3-(噻吩-2-基甲基)-3,4-二氢-2H-吡喃-2- 酮(I19)
[α]D25 ＝-262.1(c＝0.5,CHCl3).
1H NMR(400MHz,CDCl3)δ7.40-7.30(m,5H),7.29-7.27(m,3H),7.20(dd,J＝ 5.1,1.0Hz,1H),7.17-7.12(m,2H),7.06(s,1H),6.96(dd,J＝5.1,3.4Hz,1H),6.76 (d,J＝3.4Hz,1H),3.73(d,J＝6.6Hz,1H),3.50-3.26(m,2H),2.78-2.55(m,1H).
13C NMR(101MHz,CDCl3)δ168.3,144.7,140.6,135.9,131.4(2C),129.1(2C),128.5,128.3(C),128.3(2C),128.2,127.0,126.2,124.1,122.5,108.6,92.8,83.6, 45.7,45.0,26.8.
HRMS(ESI,m/z):Mass calcd.for C24H19O2S[M+H]+,371.1100；found:371.1101.
HPLC analysis:>99％e.e.(Chiralcel OD-H,25℃,IPA/Hexane＝1/99,0.5mL/min, 254nm),Rt(major)＝31.7min,Rt(minor)＝37.4min.
制备实施例20
取代基所述的R1中的取代基为乙基，制备实施方法和条件同制备实施例1。 (3S，4R)-3-叔丁基-4-苯基-5-(苯基乙炔基)-3,4-二氢-2H-吡喃-2-酮(I20)
[α]D25 ＝-73.6(c＝0.5,CHCl3).
1H NMR(400MHz,CDCl3)δ7.38-7.33(m,3H),7.33-7.26(m,5H),7.21-7.14(m, 2H),7.07(s,1H),3.73(d,J＝7.0Hz,1H),3.01-2.96(m,1H),1.83-1.63(m,1H), 1.46-1.13(m,5H),0.87(t,J＝7.2Hz,3H).
13C NMR(101MHz,CDCl3)δ169.2,144.9,136.4,131.4(2C),129.0(2C),128.4,128.3(2C),128.0(3C),122.7,108.4,92.6,83.9,45.8,43.7,29.4,26.2,22.5,13.9.
HRMS(ESI,m/z):Mass calcd.for C23H23O2[M+H]+,331.1693；found:331.1693.
HPLC analysis:98％e.e.(Chiralcel OD-H,25℃,IPA/Hexane＝1/99,0.5mL/min, 254nm),Rt(minor)＝18.4min,Rt(major)＝23.2min.
制备实施例21
取代基所述的R1中的取代基为甲基，制备实施方法和条件同制备实施例1。 (3S，4R)-3-乙基-4-苯基-5-(苯基乙炔基)-3,4-二氢-2H-吡喃-2-酮(I21)
[α]D25 ＝-35.8(c＝0.5,CHCl3).
1H NMR(400MHz,CDCl3)δ7.39-7.32(m,3H),7.32-7.26(m,5H),7.21-7.15(m, 2H),7.07(s,1H),3.76(d,J＝7.0Hz,1H),2.96-2.86(m,1H),1.87-1.72(m,1H), 1.30-1.16(m,1H),1.02(t,J＝7.4Hz,3H).
13C NMR(101MHz,CDCl3)δ169.0,145.0,136.4,131.4(2C),129.0(2C),128.4,128.3(2C),128.0(3C),122.7,108.4,92.7,83.9,45.6,45.3,19.9,11.9.
HRMS(ESI,m/z):Mass calcd.for C21H19O2[M+H]+,303.1380；found:303.1375.
HPLC analysis:>99％e.e.(Chiralcel OD-H,25℃,IPA/Hexane＝1/99,0.5mL/min, 254nm),Rt(minor)＝22.4min,Rt(major)＝24.5min.
制备实施例22
取代基所述的R2中的取代基苯环为对位甲基,制备实施方法和条件同制备实施例1。
(3S，4R)-3-苄基-5-(苯基乙炔基)-4-(对甲苯基)-3,4-二氢-2H-吡喃-2-酮(I22)
[α]D25 ＝-232.4(c＝0.5,CHCl3).
1H NMR(400MHz,CDCl3)δ7.35-7.26(m,5H),7.24(m,3H),7.16(d,J＝8.0Hz, 2H),7.11(d,J＝7.1Hz,2H),7.04-6.96(m,3H),3.52(d,J＝6.9Hz,1H),3.42-3.36 (m,1H),3.26(dd,J＝14.6,4.7Hz,1H),2.43(dd,J＝14.6,9.5Hz,1H),2.35(s,3H).
13C NMR(101MHz,CDCl3)δ169.0,144.6,138.3,137.9,133.3,131.4(2C),129.8(2C),129.1(2C),128.6(2C),128.4,128.3(2C),128.2(2C),126.7,122.6,108.9,92.7,83.8,45.2,44.7,32.3,21.2.
HRMS(ESI,m/z):Mass calcd.for C27H23O2[M+H]+,379.1693；found:379.1693.
HPLC analysis:>99％e.e.(Chiralcel OD-H,25℃,IPA/Hexane＝1/99,0.7mL/min, 254nm),Rt(major)＝21.7min,Rt(minor)＝30.0min.
制备实施例23
取代基所述的R2中的取代基为苯环对位甲氧基,制备实施方法和条件同制备实施例1。
(3S，4R)-3-苄基-4-(4-甲氧基苯基)-5-(苯基乙炔基)-3,4-二氢-2H-吡喃-2- 酮(I23)
[α]D25 ＝-171.2(c＝0.5,CHCl3).
1H NMR(400MHz,CDCl3)δ7.24-7.18(m,4H),7.17-7.10(m,4H),7.04-6.96(m, 2H),6.94-6.87(m,3H),6.81-6.72(m,2H),3.68(s,3H),3.40(d,J＝6.9Hz,1H), 3.31-3.26(m,1H),3.16(dd,J＝14.6,4.7Hz,1H),2.33(dd,J＝14.6,9.6Hz,1H).
13C NMR(101MHz,CDCl3)δ168.0,158.3,143.4,137.3,130.3(2C),128.3(2C),128.0(2C),127.6(2C),127.4,127.2(2C),127.2,125.6,121.5,113.3(2C),107.9, 91.7,82.8,54.2,44.2,43.2,31.2.
HRMS(ESI,m/z):Mass calcd.for C27H23O3[M+H]+,395.1642；found:395.1640.
HPLC analysis:>99％e.e.(Chiralcel IA,25℃,IPA/Hexane＝1/99,0.7mL/min,254nm),Rt(major)＝20.8min,Rt(minor)＝24.6min.
制备实施例24
取代基所述的R2中的取代基为对位-Cl。制备实施方法和条件同制备实施例 1。
(3S，4R)-3-苄基-4-(4-氯苯基)-5-(苯基乙炔基)-3,4-二氢-2H-吡喃-2-酮(I24)
[α]D25 ＝-343.4(c＝0.5,CHCl3).
1H NMR(400MHz,CDCl3)δ7.37-7.26(m,9H),7.24(dd,J＝3.7,2.4Hz,1H), 7.09(d,J＝7.0Hz,2H),7.06-6.99(m,3H),3.53(d,J＝7.0Hz,1H),3.46-2.40(m, 1H),3.29(dd,J＝14.7,4.7Hz,1H),2.40(dd,J＝14.7,9.7Hz,1H).
13C NMR(101MHz,CDCl3)δ168.6,144.8,137.8,134.9,134.1,131.4(2C),129.7(2C),129.3(2C),129.0(2C),128.8(2C),128.6,128.4(2C),126.9,122.4,108.4,93.1,83.3,44.8,44.5,32.3.
HRMS(ESI,m/z):Mass calcd.for C26H20O2Cl[M+H]+,399.1146；found:399.1144.
HPLC analysis:99％e.e.(Chiralcel IA,25℃,IPA/Hexane＝1/99,0.7mL/min,254 nm),Rt(major)＝15.0min,Rt(minor)＝17.1min.
制备实施例25
取代基所述的R2中的取代基为苯环对位三氟甲基，制备实施方法和条件同制备实施例1。
(3S，4R)-3-苄基-5-(苯基乙炔基)-4-(4-(三氟甲基)苯基)-3,4-二氢-2H- 吡喃-2-酮(I25)
[α]D25 ＝-173.8(c＝0.5,CHCl3).
1H NMR(400MHz,CDCl3)δ7.36-7.26(m,7H),7.26-7.22(m,1H),7.12-7.01(m, 7H),3.54(d,J＝7.0Hz,1H),3.46-3.40(m,1H),3.29(dd,J＝14.7,4.7Hz,1H),2.40 (dd,J＝14.7,9.7Hz,1H).
13C NMR(101MHz,CDCl3)δ168.7,162.51(d,J＝247.0Hz),144.7,137.9,132.2,132.1,131.4(2C),130.0,129.9,129.0(2C),128.7(2C),128.6,128.3(2C),126.8, 122.4,116.2,115.9,108.6,93.0,83.4,44.9,44.3,32.3.
19F NMR(376MHz,CDCl3)δ-113.8.
HRMS(ESI,m/z):Mass calcd.for C27H19O3F3[M+H]+,432.1332；found:432.1335.
HPLC analysis:>99％e.e.(Chiralcel OD-H,25℃,IPA/Hexane＝1/99,0.5mL/min, 254nm),Rt(major)＝35.0min,Rt(minor)＝42.1min.
制备实施例26
取代基所述的R2中的取代基为间位卤原子,制备实施方法和条件同制备实施例1。
(3S，4R)-3-苄基-4-(3-氯苯基)-5-(苯基乙炔基)-3,4-二氢-2H-吡喃-2-酮(I26)
[α]D25 ＝-139.7(c＝1.0,CHCl3).
1H NMR(400MHz,CDCl3)δ7.28(s,1H),7.24-7.14(m,9H),7.02(d,J＝7.3Hz, 2H),6.98(s,2H),6.92(d,J＝6.3Hz,1H),3.52-3.41(m,1H),3.41-3.31(m,1H), 3.29-3.15(m,1H),2.33(dd,J＝14.8,9.7Hz,1H).
13C NMR(101MHz,CDCl3)δ167.4,144.0,137.3,136.7 133.7,130.3(2C),129.4,127.9(2C),127.7(3C),127.6,127.4,127.3(2C),125.8,125.1,121.3,107.0,92.0, 82.2,43.7,43.7,31.2.
HRMS(ESI,m/z):Mass calcd.for C26H20O2Cl[M+H]+,399.1146；found:399.1145.
HPLC analysis:98％e.e.(Chiralcel IA,25℃,IPA/Hexane＝1/99,0.3mL/min,254 nm),Rt(major)＝31.3min,Rt(minor)＝33.5min.
制备实施例27
取代基所述的R2中的取代基为苯环间位卤原子,制备实施方法和条件同制备实施例1。
(3S，4S)-3-苄基-4-(2-氯苯基)-5-(苯基乙炔基)-3,4-二氢-2H-吡喃-2-酮(I27)
[α]D25 ＝-262.1(c＝0.5,CHCl3).
1H NMR(400MHz,CDCl3)δ7.42(dd,J＝7.7,1.6Hz,1H),7.38-7.26(m,9H), 7.25-7.15(m,2H),7.05(d,J＝7.1Hz,2H),7.01(s,1H),4.47(s,1H),3.49-3.43(m,J ＝7.9,6.1Hz,1H),3.23-3.12(m,1H),2.54(dd,J＝14.5,8.1Hz,1H).
13C NMR(101MHz,CDCl3)δ168.8,146.3,144.7,138.0,134.7,131.3(2C),130.2,129.5,129.2,129.0(2C),128.7(2C),128.5,128.3(2C),128.0,126.7,122.6,103.2,93.1,83.3,47.5,44.9,32.5.
HRMS(ESI,m/z):Mass calcd.for C26H20O2Cl[M+H]+,399.1146；found:399.1143.
HPLC analysis:>99％e.e.(Chiralcel OD-H,25℃,IPA/Hexane＝1/99,1.0mL/min, 254nm),Rt(major)＝13.1min,Rt(minor)＝17.6min.
制备实施例28
取代基所述的R2中的取代基为噻吩。制备实施方法和条件同制备实施例1。 (3S，4S)-3-苄基-5-(苯基乙炔基)-4-(噻吩-2-基)-3,4-二氢-2H-吡喃-2-酮(I28)
[α]D25 ＝-189.9(c＝1.0,CHCl3).
1H NMR(400MHz,CDCl3)δ7.38-7.30(m,4H),7.28(dd,J＝5.1,3.3Hz,4H), 7.25(s,1H),7.22-7.14(m,2H),7.05-6.96(m,2H),6.89(dd,J＝3.5,0.6Hz,1H), 3.83(d,J＝6.2Hz,1H),3.45-3.29(m,2H),2.72-2.48(m,1H).
13C NMR(101MHz,CDCl3)δ167.4,143.7,137.5,137.0,130.4(2C),128.1(2C),127.7(2C),127.5,127.3(2C),126.3,125.8,125.4,124.3,121.4,108.0,92.4,82.2,44.9,38.8,31.2.
HRMS(ESI,m/z):Mass calcd.for C24H19O2S[M+H]+,371.1100；found:371.1098.
HPLC analysis:>99％e.e.(Chiralcel OD-H,25℃,IPA/Hexane＝1/99,0.7mL/min, 254nm),Rt(major)＝37.0min,Rt(minor)＝54.0min.
制备实施例29
取代基所述的R2中的取代基为呋喃。制备实施方法和条件同制备实施例1。 (3S，4S)-3-苄基-4-(呋喃-2-基)-5-(苯基乙炔基)-3,4-二氢-2H-吡喃-2-酮(I29)
[α]D25 ＝-158.7(c＝0.5,CHCl3).
1H NMR(400MHz,CDCl3)δ7.47-7.40(m,1H),7.38-7.31(m,4H),7.31-7.26(m, 4H),7.23-7.14(m,2H),7.00(s,1H),6.37(dd,J＝3.2,1.9Hz,1H),6.22(d,J＝3.2 Hz,1H),3.61(d,J＝6.5Hz,1H),3.40(dd,J＝14.4,4.1Hz,1H),3.27-3.22(m,1H), 2.43(dd,J＝14.4,10.4Hz,1H).
13C NMR(101MHz,CDCl3)δ168.3,149.7,145.7,143.1,138.1,131.4(2C),129.2(2C),128.7(2C),128.6,128.4(2C),126.8,122.5,110.5,109.2,105.7,92.9,83.3, 44.6,38.1,32.5.
HRMS(ESI,m/z):Mass calcd.for C24H19O3[M+H]+,355.1329；found:355.1324.
HPLC analysis:>99％e.e.(Chiralcel OD-H,25℃,IPA/Hexane＝1/99,0.7mL/min, 254nm),Rt(major)＝31.3min,Rt(minor)＝41.7min.
制备实施例30
取代基所述的R3中的取代基为苯环对位-F,制备实施方法和条件同制备实施例1。
(3S，4R)-3-苄基-5-((4-氟苯基)乙炔基)-4-苯基-3,4-二氢-2H-吡喃-2-酮(I30)
[α]D25 ＝-263.4(c＝0.5,CHCl3).
1H NMR(400MHz,CDCl3)δ7.39-7.27(m,7H),7.26-7.23(m,1H),7.10(dd,J＝ 7.9,1.3Hz,4H),7.03(s,1H),6.99-6.89(m,2H),3.54(d,J＝7.0Hz,1H),3.44-3.99 (m,1H),3.27(dd,J＝14.7,4.7Hz,1H),2.42(dd,J＝14.7,9.6Hz,1H).
13C NMR(101MHz,CDCl3)δ168.8,162.6(d,J＝250.1Hz),144.7,138.2,136.4,133.4,133.3,129.1(2C),129.0(2C),128.7(2C),128.3(2C),128.2,126.7,118.7(d, J＝3.5Hz),115.8,115.5,108.6,91.7,83.4,45.1,45.0,32.3.
19F NMR(376MHz,CDCl3)δ-110.4.
HRMS(ESI,m/z):Mass calcd.for C26H20O2F[M+H]+,383.1442；found:383.1443.
HPLC analysis:99％e.e.(Chiralcel IA,25℃,IPA/Hexane＝1/99,1.0mL/min,254 nm),Rt(major)＝9.8min,Rt(minor)＝11.1min.
制备实施例31
取代基所述的R3中的取代基为苯环对位-Cl，制备实施方法和条件同制备实施例1。
(3S，4R)-3-苄基-5-((4-氯苯基)乙炔基)-4-苯基-3,4-二氢-2H-吡喃-2-酮(I31)
[α]D25 ＝-148.0(c＝0.5,CHCl3).
1H NMR(400MHz,CDCl3)δ7.40-7.30(m,5H),7.28(d,J＝1.2Hz,1H),7.23(s, 4H),7.10(d,J＝7.8Hz,4H),7.05(s,1H),3.55(d,J＝7.0Hz,1H),3.45-4.39(m, 1H),3.28(dd,J＝14.7,4.7Hz,1H),2.42(dd,J＝14.7,9.6Hz,1H).
13C NMR(101MHz,CDCl3)δ168.8,145.0,138.1,136.3,134.5,132.6(2C),129.1(2C),129.0(2C),128.7(2C),128.6(2C),128.3(2C),128.2,126.7,121.1,108.5,91.7,84.7,45.1,45.0,32.3.
HRMS(ESI,m/z):Mass calcd.for C26H20O2Cl[M+H]+,399.1146；found:399.1148.
HPLC analysis:97％e.e.(Chiralcel IA,25℃,IPA/Hexane＝1/99,0.5mL/min,254 nm),Rt(major)＝20.3min,Rt(minor)＝24.8min.
制备实施例32
取代基所述的R3中的取代基为苯环对位三氟甲基，制备实施方法和条件同制备实施例1。
(3S，4R)-3-苄基-4-苯基-5-((4-(三氟甲基)苯基)乙炔基)-3,4-二氢-2H-吡喃-2-酮(I32)
[α]D25 ＝-165.0(c＝1.0,CHCl3).
1H NMR(400MHz,CDCl3)δ7.53(d,J＝8.2Hz,2H),7.47–7.29(m,8H),7.12 (dd,J＝10.4,3.4Hz,5H),3.59(d,J＝7.0Hz,1H),3.45(m,1H),3.31(dd,J＝14.7, 4.7Hz,1H),2.46(dd,J＝14.7,9.6Hz,1H).
13C NMR(101MHz,CDCl3)δ168.6,145.5,143.0,138.1,136.2,131.6(2C),130.4,130.3,129.1(2C),129.0(2C),128.7(2C),128.3,128.3(2C),126.8,126.4,125.2(dd, J＝7.7,3.7Hz),108.2,91.4,86.2,45.1,45.0,32.3.
19F NMR(377MHz,CDCl3)δ-62.9.
HRMS(ESI,m/z):Mass calcd.for C27H20O2F3[M+H]+,433.1410；found:433.1411.
HPLC analysis:99％e.e.(Chiralcel IA,25℃,IPA/Hexane＝1/99,0.5mL/min,254 nm),Rt(major)＝21.6min,Rt(minor)＝23.4min.
制备实施例33
取代基所述的R3中的取代基为苯环对位甲基，制备实施方法和条件同制备实施例1。
(3S，4R)-3-苄基-4-苯基-5-(对甲苯基乙炔基)-3,4-二氢-2H-吡喃-2-酮(I33)
[α]D25 ＝-226.1(c＝0.5,CHCl3).
1H NMR(400MHz,CDCl3)δ7.39-7.28(m,5H),7.24(d,J＝8.1Hz,1H),7.19(d,J ＝8.1Hz,2H),7.09(m,6H),7.01(s,1H),3.54(d,J＝7.0Hz,1H),3.43-3.38(m,1H), 3.27(dd,J＝14.7,4.7Hz,1H),2.42(dd,J＝14.7,9.6Hz,1H),2.30(s,3H).
13C NMR(101MHz,CDCl3)δ169.0,144.4,138.7,138.2,136.5,131.3(2C),129.1(4C),129.0(2C),128.7(2C),128.3(2C),128.1,126.7,119.5,108.9,93.0,83.0,45.1,45.1,32.3,21.5.
HRMS(ESI,m/z):Mass calcd.for C27H23O2[M+H]+,379.1693；found:379.1690.
HPLC analysis:95％e.e.(Chiralcel OD-H,25℃,IPA/Hexane＝1/99,0.7mL/min, 254nm),Rt(major)＝29.5min,Rt(minor)＝36.5min.
制备实施例34
取代基所述的R3中的取代基为苯环对位甲氧基，制备实施方法和条件同制备实施例1。
(3S，4R)-3-苄基-5-((4-甲氧基苯基)乙炔基)-4-苯基-3,4-二氢-2H-吡喃-2- 酮(I34)
[α]D25 ＝-174.2(c＝1.0,CHCl3).
1H NMR(400MHz,CDCl3)δ7.39-7.26(m,5H),7.26-7.22(m,3H),7.14-7.04(m, 4H),7.00(s,1H),6.80-6.72(m,2H),3.76(s,3H),3.53(d,J＝7.0Hz,1H),3.43-3.38 (m,1H),3.26(dd,J＝14.6,4.7Hz,1H),2.41(dd,J＝14.7,9.6Hz,1H).
13C NMR(101MHz,CDCl3)δ169.0,159.7,144.1,138.2,136.5,132.8(2C),129.0(2C),129.0(2C),128.6(2C),128.3(2C),128.1,126.7,114.6,113.9(2C),109.0,92.8,82.28,55.3,45.1,45.1,32.2.
HRMS(ESI,m/z):Mass calcd.for C27H23O3[M+H]+,395.1642；found:395.1643.
HPLC analysis:99％e.e.(Chiralcel IA,25℃,IPA/Hexane＝1/99,0.5mL/min,254 nm),Rt(major)＝28.1min,Rt(minor)＝33.6min.
制备实施例35
取代基所述的R3中的取代基为苯环邻位甲氧基，制备实施方法和条件同制备实施例1。
(3S，4R)-3-苄基-5-((3-甲氧基苯基)乙炔基)-4-苯基-3,4-二氢-2H-吡喃-2- 酮(I35)
[α]D25 ＝-194.5(c＝1.0,CHCl3).
1H NMR(400MHz,CDCl3)δ7.39-7.29(m,5H),7.26(d,J＝7.2Hz,1H),7.19-7.07 (m,5H),7.04(s,1H),6.92-6.89(m,1H),6.86-6.78(m,2H),3.75(s,3H),3.55(d,J＝ 7.0Hz,1H),3.44-3.39(m,1H),3.27(dd,J＝14.7,4.7Hz,1H),2.42(dd,J＝14.7, 9.6Hz,1H).
13C NMR(101MHz,CDCl3)δ168.9,159.2,144.8,138.2,136.4,129.4,129.1(2C),129.1(2C),128.7(2C),128.3(2C),128.2,126.7,124.0,123.5,116.2,115.1,108.7,92.7,83.5,55.3,45.1,45.0,32.3.
HRMS(ESI,m/z):Mass calcd.for C27H23O3[M+H]+,395.1642；found:395.1642.
HPLC analysis:96％e.e.(Chiralcel IA,25℃,IPA/Hexane＝1/99,0.5mL/min,254 nm),Rt(major)＝23.7min,Rt(minor)＝31.2min.
制备实施例36
取代基所述的R3中的取代基为苯环间位卤原子，制备实施方法和条件同制备实施例1。
(3S，4R)-3-苄基-5-((3-氟苯基)乙炔基)-4-苯基-3,4-二氢-2H-吡喃-2-酮(I36)
[α]D 25＝-184.7(c＝1.0,CHCl3).
1H NMR(400MHz,CDCl3)δ7.44-7.26(m,6H),7.25-7.16(m,1H),7.12-7.06(m, 6H),7.02-6.96(m,2H),3.56(d,J＝7.0Hz,1H),3.46-3.40(m,1H),3.29(dd,J＝ 14.7,4.7Hz,1H),2.43(dd,J＝14.7,9.6Hz,1H).
13C NMR(101MHz,CDCl3)δ168.8,162.3(d,J＝246.8Hz),145.2,138.1,136.3,129.9(d,J＝8.7Hz),129.2(2C),129.1(2C),128.7(2C),128.3(2C),128.3,127.3(d, J＝3.0Hz),126.8,124.5(d,J＝9.5Hz),118.2(d,J＝22.9Hz),115.8(d,J＝21.2 Hz),108.4,91.6,84.7,45.1,45.0,32.3.
19F NMR(376MHz,CDCl3)δ-112.8.
HRMS(ESI,m/z):Mass calcd.for C26H20O2F[M+H]+,383.1442；found:383.1442.
HPLC analysis:99％e.e.(Chiralcel OD-H,25℃,IPA/Hexane＝1/99,0.3mL/min, 254nm),Rt(minor)＝36.6min,Rt(major)＝41.7min.
制备实施例37
取代基所述的R3中的取代基为苯环间位甲氧基，制备实施方法和条件同制备实施例1。
(3S，4R)-3-苄基-4-苯基-5-(噻吩-2-基乙炔基)-3,4-二氢-2H-吡喃-2-酮(I37)
[α]D25 ＝-216.5(c＝0.5,CHCl3).
1H NMR(400MHz,CDCl3)δ7.40-7.28(m,5H),7.26(s,1H),7.24(d,J＝5.5,1.7 Hz,2H),7.15-7.08(m,4H),7.05(s,1H),6.88-6.80(m,2H),3.81(s,3H),3.59(d,J＝7.0Hz,1H),3.45-3.40(m,1H),3.29(dd,J＝14.6,4.8Hz,1H),2.45(dd,J＝14.6, 9.5Hz,1H).
13C NMR(101MHz,CDCl3)δ169.1,159.7,144.4,138.2,136.6,133.3,130.0,129.1(2C),129.0(2C),128.6(2C),128.4(2C),128.1,126.7,120.4,111.8,110.6,109.0, 89.3,87.7,55.7,45.2,45.0,32.3.
HRMS(ESI,m/z):Mass calcd.for C27H23O3[M+H]+,395.1642；found:395.1642.
HPLC analysis:>99％e.e.(Chiralcel OD-H,25℃,IPA/Hexane＝1/99,0.5mL/min, 254nm),Rt(major)＝12.9min,Rt(minor)＝47.5min.
制备实施例38
取代基所述的R3中的取代基为噻吩，制备实施方法和条件同制备实施例1。 (3S，4R)-3-苄基-4-苯基-5-(噻吩-2-基乙炔基)-3,4-二氢-2H-吡喃-2-酮(I38)
[α]D25 ＝-280.7(c＝0.5,CHCl3).
1H NMR(400MHz,CDCl3)δ7.40-7.25(m,6H),7.24-7.19(m,1H),7.13-7.07(m, 5H),7.03(s,1H),6.92(dd,J＝5.1,3.7Hz,1H),3.55(d,J＝6.9Hz,1H),3.43-3.38 (m,1H),3.26(dd,J＝14.7,4.7Hz,1H),2.42(dd,J＝14.7,9.6Hz,1H).
13C NMR(101MHz,CDCl3)δ168.8,144.9,138.1,136.3,132.1,129.1(2C),129.0(2C),128.7(2C),128.3(2C),128.2,127.8,127.1,126.8,122.6,108.6,87.3,85.9, 45.1,44.9,32.3.
HRMS(ESI,m/z):Mass calcd.for C24H19O2S[M+H]+,371.1100；found:371.1100.
HPLC analysis:96％e.e.(Chiralcel OD-H,25℃,IPA/Hexane＝1/99,0.5mL/min, 254nm),Rt(major)＝50.8min,Rt(minor)＝58.9min.
制备实施例39
取代基所述的R3中的取代基为环丙烷，制备实施方法和条件同制备实施例1。(3S，4R)-3-苄基-5-(环丙基乙炔基)-4-苯基-3,4-二氢-2H-吡喃-2-酮(I39)
[α]D 25＝-200.8(c＝1.0,CHCl3).
1H NMR(400MHz,CDCl3)δ7.38-7.32(m,3H),7.32-7.27(m,2H),7.24(dd,J＝ 6.2,3.4Hz,1H),7.11-7.00(m,4H),6.85(s,1H),3.43-3.28(m,2H),3.23(dd,J＝ 14.6,4.5Hz,1H),2.36(dd,J＝14.6,9.3Hz,1H),1.27-1.20(m,1H),0.80-0.68(m, 2H),0.67-0.53(m,2H).
13C NMR(101MHz,CDCl3)δ169.1,143.9,138.2,136.4,128.9(2C),128.8(2C),128.5(2C),128.2(2C),127.9,126.5,109.0,97.0,69.8,45.1,44.9,32.1,8.5,8.5,0.1.
HRMS(ESI,m/z):Mass calcd.for C23H21O2[M+H]+,329.1536；found:329.1536.
HPLC analysis:99％e.e.(Chiralcel OD-H,25℃,IPA/Hexane＝1/99,0.5mL/min, 254nm),Rt(minor)＝21.9min,Rt(major)＝23.9min.
制备实施例40
取代基所述的R1为对位-Br,R3中的取代基为环丙烷。制备实施方法和条件同制备实施例1。
(3S，4R)-3-(4-溴苄基)-5-(环丙基乙炔基)-4-苯基-3,4-二氢-2H-吡喃-2-酮(I40)
[α]D25 ＝-195.2(c＝0.5,CHCl3).
1H NMR(400MHz,CDCl3)δ7.47–7.38(m,2H),7.38–7.28(m,3H),7.06–6.99 (m,2H),6.94(d,J＝8.3Hz,2H),6.84(s,1H),3.35(d,J＝7.0Hz,1H),3.27(m,1H), 3.14(dd,J＝14.7,5.0Hz,1H),2.34(dd,J＝14.7,9.2Hz,1H),1.24(m,1H),0.74(m, 2H),0.61(m,2H).
13C NMR(101MHz,CDCl3)δ168.8,143.9,137.3,136.3,131.7(2C),130.7(2C),129.0(2C),128.2(2C),128.1,120.5,109.0,97.3,69.8,45.4,44.8,31.9,8.6,8.6,0.1.
HRMS(ESI,m/z):Mass calcd.for C23H20O2Br[M+H]+,407.0641；found:407.0639.
HPLC analysis:>99％e.e.(Chiralcel OD-H,25℃,IPA/Hexane＝1/99,0.8mL/min, 254nm),Rt(minor)＝14.5min,Rt(major)＝24.9min.
制备实施例41
取代基所述的R3中的取代基为叔丁基，制备实施方法和条件同制备实施例1。(3S，4R)-3-苄基-5-(3,3-二甲基丁-1-炔-1-基)-4-苯基-3,4-二氢-2H-吡喃-2-酮 (I41)
[α]D25 ＝-174.8(c＝1.0,CHCl3).
1H NMR(400MHz,CDCl3)δ7.29-7.27(m,1H),7.26-7.12(m,5H),7.05-6.93(m, 4H),6.75(s,1H),3.34-3.22(m,2H),3.18(dd,J＝14.5,4.4Hz,1H),2.34(dd,J＝14.5,8.8Hz,1H),1.05(s,9H).
13C NMR(101MHz,CDCl3)δ168.3,142.3,137.3,135.7,128.0(2C),127.9(2C),127.5(2C),127.2(2C),126.8,125.5,108.0,101.2,72.2,44.4,43.8,31.3,29.7(3C),26.9.
HRMS(ESI,m/z):Mass calcd.for C24H25O2[M+H]+,345.1849；found:345.1848.
HPLC analysis:99％e.e.(Chiralcel IC,25℃,IPA/Hexane＝4/96,1.0mL/min,254 nm),Rt(minor)＝5.4min,Rt(major)＝6.7min.
制备实施例42
取代基所述的R3中的取代基为正丁烷，制备实施方法和条件同制备实施例1。(3S，4R)-3-苄基-5-(2-丁基-乙炔基)-4-苯基-3,4-二氢-2H-吡喃-2-酮(I42)
[α]D25 ＝-203.8(c＝1.0,CHCl3).
1H NMR(400MHz,CDCl3)δ7.38-7.26(m,5H),7.25-7.22(m,1H),7.13-6.97(m, 4H),6.86(s,1H),3.40(d,J＝7.0Hz,1H),3.37-3.32(m,1H),3.24(dd,J＝14.6,4.6 Hz,1H),2.38(dd,J＝14.6,9.3Hz,1H),2.19(t,J＝7.0Hz,2H),1.46-1.35(m,2H), 1.35-1.22(m,2H),0.84(t,J＝7.3Hz,3H).
13C NMR(101MHz,CDCl3)δ169.2,143.7,138.3,136.6,129.0(2C),128.9(2C),128.6(2C),128.3(2C),128.0,126.6,109.1,94.1,74.7,45.3,45.0,32.2,30.5,21.9,19.1,13.5.
HRMS(ESI,m/z):Mass calcd.for C24H25O2[M+H]+,345.1849；found:345.1848.
HPLC analysis:>99％e.e.(Chiralcel ID,25℃,IPA/Hexane＝2/98,0.3mL/min,254nm),Rt(minor)＝19.8min,Rt(major)＝21.7min.
制备实施例43
取代基所述的R3中的取代基为氢原子。制备实施方法和条件同制备实施例1。
[α]D25 ＝-370.9(c＝1.0,CHCl3).
1H NMR(400MHz,CDCl3)δ7.39-7.30(m,4H),7.29(d,J＝1.2Hz,1H),7.25-7.23 (m,1H),7.09-7.04(m,4H),7.02-6.99(m,1H),3.47(d,J＝7.0Hz,1H),3.41-3.31(m, 1H),3.24(dd,J＝14.7,4.7Hz,1H),2.92(s,1H),2.38(dd,J＝14.7,9.5Hz,1H).
13C NMR(101MHz,CDCl3)δ168.7,146.1,138.0,136.1,129.1(2C),129.0(2C),128.7(2C),128.3(3C),126.8,107.6,80.9,78.3,45.0,44.8,32.2.
HRMS(ESI,m/z):Mass calcd.for C20H17O2[M+H]+,289.1223；found:289.1221.
HPLC analysis:>99％e.e.(Chiralcel IA,25℃,IPA/Hexane＝1/99,1.0mL/min,254nm),Rt(major)＝10.1min,Rt(minor)＝11.5min.
制备实施例44
取代基所述的R3中的取代基为三甲基硅烷，制备实施方法和条件同制备实施例1。
(3S，4R)-3-苄基-4-苯基-5-((三甲基甲硅烷基)乙炔基)-3,4-二氢-2H-吡喃-2-酮(I44)
[α]D25 ＝-242.9(c＝1.0,CHCl3).
1H NMR(400MHz,CDCl3)δ7.38-7.27(m,5H),7.25-7.21(m,1H),7.11-7.02(m, 4H),6.96(s,1H),3.44(d,J＝7.0Hz,1H),3.36-3.31(m,1H),3.24(dd,J＝14.6,4.7 Hz,1H),2.40(dd,J＝14.6,9.4Hz,1H),0.10(s,9H).
13C NMR(101MHz,CDCl3)δ169.1,145.8,138.4,136.5,129.3(2C),129.2(2C),128.8(2C),128.5(2C),128.3,126.9,108.9,99.4,98.7,45.1,45.1,32.5,0.0(3C).
HRMS(ESI,m/z):Mass calcd.for C23H24O2Si[M+H]+,361.1618；found:361.1616.
HPLC analysis:99％e.e.(Chiralcel IC,25℃,IPA/Hexane＝1/99,1.0mL/min,254 nm),Rt(minor)＝7.1min,Rt(major)＝10.5min.
制备实施例45
取代基所述的R3中的取代均三甲苯。制备实施方法和条件同制备实施例1。
无色黏状物，产率：37％yield.
[α]D25 ＝-125.0(c＝1.0,CHCl3).
1H NMR(400MHz,CDCl3)δ7.41–7.30(m,5H),7.26(dd,J＝7.8,1.7Hz,1H), 7.13(dd,J＝7.7,1.4Hz,4H),7.03(s,1H),6.81(s,2H),3.60(d,J＝7.2Hz,1H), 3.47(m,1H),3.30(dd,J＝14.7,4.9Hz,1H),2.54–2.40(m,1H),2.25(s,3H),2.23 (s,6H).
13C NMR(101MHz,CDCl3)δ169.0,143.5,139.8(2C),138.3,138.0,136.7,129.0(4C),128.6(2C),128.4(2C),128.1,127.6(3C),126.7,119.3,109.3,91.1,45.8,45.0,32.4,21.3,20.8(2C).
HRMS(ESI,m/z):Mass calcd.for C29H27O2[M+H]+,407.2006；found:407.2002.
HPLC analysis:81％e.e.(Chiralcel IF,25℃,IPA/Hexane＝4/96,0.5mL/min,254 nm),Rt(major)＝14.0min,Rt(minor)＝15.5min.
制备实施例46
取代基所述的R3中的取代为2,6-二异丙基苯。制备实施方法和条件同制备实施例1。
(3S，4R)-3-苄基-5-((2,6-二异丙基苯基)乙炔基)-4-苯基-3,4-二氢-2H-吡喃 -2-酮(I46)
[α]D25 ＝-203.0(c＝1.0,CHCl3).
1H NMR(400MHz,CDCl3)δ7.39–7.29(m,5H),7.22(dd,J＝16.9,9.1Hz,2H), 7.11(m,4H),7.05–7.00(m,3H),3.61(d,J＝7.2Hz,1H),3.47(m,1H),3.27(dd,J ＝14.7,5.0Hz,1H),3.24–3.11(m,2H),2.45(dd,J＝14.7,9.2Hz,1H),1.14(s,3H), 1.12(s,3H),1.07(s,3H),1.05(s,3H).
13C NMR(101MHz,CDCl3)δ168.9,150.5(2C),143.6(2C),138.3,136.7,129.0(4C),128.6,128.6(2C),128.4(2C),128.1,126.7,122.1,120.2,109.2,91.5,90.3, 45.9,45.0,32.4,31.7(2C),23.1(2C),23.0(2C).
HRMS(ESI,m/z):Mass calcd.for C32H33O2[M+H]+,449.2475；found:449.2466.
HPLC analysis:80％e.e.(Chiralcel ODH,25℃,IPA/Hexane＝2/98,0.6mL/min,254nm),Rt(major)＝11.1min,Rt(minor)＝10.0min。
Claims (7)
1.一种氮杂环卡宾催化合成包含1,3-烯炔官能团的二氢吡喃酮类化合物，其特征在于：所述的衍生物如通式(1)表示：
其中，R1为苯基、取代苯、萘、呋喃、噻吩或烷基；R2为苯基、取代苯、呋喃或噻吩；R3为苯基、取代苯、噻吩或烷基。
2.根据权利要求1所述的化合物，其特征在于：所述的R1中的取代苯的取代基为对位、邻位、间位中的一个或一个以上取代，苯环邻位取代基为卤原子、甲基或甲氧基；或苯环间位取代基为卤原子、甲基或三氟甲基；或苯环对位取代基为卤原子、甲基、氰基或三氟甲氧基。
3.根据权利要求1所述的化合物，其特征在于：所述的R2中的取代苯的取代基为对位甲基、甲氧基、卤原子或三氟甲基，或邻位为卤原子；或间位为卤原子。
4.根据权利要求1所述的化合物，其特征在于：所述的R3中的取代苯的取代基为对位、邻位、间位中的一个或一个以上取代，苯环对位取代基为卤原子、甲基、甲氧基或三氟甲基，或苯环邻位取代基为甲氧基，或苯环间位取代基为卤原子或甲氧基。
5.如权利要求1-3之一所述的化合物的制备方法，其特征在于：反应通式及过程如下：
6.根据权利要求5所述的制备方法，其特征在于：所述的
的制备方法：
7.根据权利要求5所述的制备方法，其特征在于：反应温度为室温。
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