CN115490627A - 一种合成手性4-位偕二氟烯基取代吡咯烷酮的方法 - Google Patents
一种合成手性4-位偕二氟烯基取代吡咯烷酮的方法 Download PDFInfo
- Publication number
- CN115490627A CN115490627A CN202211162260.XA CN202211162260A CN115490627A CN 115490627 A CN115490627 A CN 115490627A CN 202211162260 A CN202211162260 A CN 202211162260A CN 115490627 A CN115490627 A CN 115490627A
- Authority
- CN
- China
- Prior art keywords
- chiral
- difluoroalkenyl
- cdcl
- nmr
- gem
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 238000000034 method Methods 0.000 title claims abstract description 26
- 150000004040 pyrrolidinones Chemical class 0.000 title claims abstract description 14
- 230000002194 synthesizing effect Effects 0.000 title claims abstract description 13
- 239000003446 ligand Substances 0.000 claims abstract description 24
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 claims abstract description 23
- 239000003054 catalyst Substances 0.000 claims abstract description 18
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 claims abstract description 10
- -1 aryl boric acid Chemical compound 0.000 claims abstract description 5
- 238000006115 defluorination reaction Methods 0.000 claims abstract description 5
- 238000007363 ring formation reaction Methods 0.000 claims abstract description 5
- 238000006254 arylation reaction Methods 0.000 claims abstract description 4
- 238000010438 heat treatment Methods 0.000 claims abstract description 4
- 229910052759 nickel Inorganic materials 0.000 claims abstract 3
- 238000006243 chemical reaction Methods 0.000 claims description 21
- OINIXPNQKAZCRL-UHFFFAOYSA-L nickel(2+);diacetate;tetrahydrate Chemical group O.O.O.O.[Ni+2].CC([O-])=O.CC([O-])=O OINIXPNQKAZCRL-UHFFFAOYSA-L 0.000 claims description 20
- 229940078487 nickel acetate tetrahydrate Drugs 0.000 claims description 19
- KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical group [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 claims description 18
- RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical group OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 claims description 16
- 150000001543 aryl boronic acids Chemical class 0.000 claims description 6
- 239000003960 organic solvent Substances 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 239000011261 inert gas Substances 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 239000002994 raw material Substances 0.000 abstract description 4
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 abstract description 3
- 239000004327 boric acid Substances 0.000 abstract description 2
- 238000006555 catalytic reaction Methods 0.000 abstract description 2
- 238000001212 derivatisation Methods 0.000 abstract 1
- 238000001308 synthesis method Methods 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 42
- 239000000758 substrate Substances 0.000 description 30
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 28
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 28
- 239000011541 reaction mixture Substances 0.000 description 26
- 238000002360 preparation method Methods 0.000 description 15
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 14
- 150000001875 compounds Chemical class 0.000 description 14
- 239000003480 eluent Substances 0.000 description 14
- 238000004128 high performance liquid chromatography Methods 0.000 description 14
- 230000003287 optical effect Effects 0.000 description 14
- 239000003208 petroleum Substances 0.000 description 14
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 14
- 238000007789 sealing Methods 0.000 description 14
- 238000010898 silica gel chromatography Methods 0.000 description 14
- 239000002904 solvent Substances 0.000 description 14
- 238000003786 synthesis reaction Methods 0.000 description 14
- 230000015572 biosynthetic process Effects 0.000 description 13
- 238000012544 monitoring process Methods 0.000 description 12
- 239000007787 solid Substances 0.000 description 11
- 239000012300 argon atmosphere Substances 0.000 description 7
- 125000006418 4-methylphenylsulfonyl group Chemical group 0.000 description 6
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical group O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 2
- 239000012230 colorless oil Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- CEBAHYWORUOILU-UHFFFAOYSA-N (4-cyanophenyl)boronic acid Chemical compound OB(O)C1=CC=C(C#N)C=C1 CEBAHYWORUOILU-UHFFFAOYSA-N 0.000 description 1
- VXWBQOJISHAKKM-UHFFFAOYSA-N (4-formylphenyl)boronic acid Chemical compound OB(O)C1=CC=C(C=O)C=C1 VXWBQOJISHAKKM-UHFFFAOYSA-N 0.000 description 1
- VDUKDQTYMWUSAC-UHFFFAOYSA-N (4-methylsulfonylphenyl)boronic acid Chemical compound CS(=O)(=O)C1=CC=C(B(O)O)C=C1 VDUKDQTYMWUSAC-UHFFFAOYSA-N 0.000 description 1
- HUOFUOCSQCYFPW-UHFFFAOYSA-N [4-(trifluoromethoxy)phenyl]boronic acid Chemical compound OB(O)C1=CC=C(OC(F)(F)F)C=C1 HUOFUOCSQCYFPW-UHFFFAOYSA-N 0.000 description 1
- ZIQCCIAIROIHHR-UHFFFAOYSA-N benzene;boric acid Chemical compound OB(O)O.C1=CC=CC=C1 ZIQCCIAIROIHHR-UHFFFAOYSA-N 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- DSSBJZCMMKRJTF-UHFFFAOYSA-N dibenzofuran-2-ylboronic acid Chemical compound C1=CC=C2C3=CC(B(O)O)=CC=C3OC2=C1 DSSBJZCMMKRJTF-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/46—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with hetero atoms directly attached to the ring nitrogen atom
- C07D207/48—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/36—Oxygen or sulfur atoms
- C07D207/38—2-Pyrrolones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
Abstract
本申请公开了一种合成手性4‑位偕二氟烯基取代吡咯烷酮的方法。该方法，是以苯硼酸、三氟甲基烯烃取代的1,6‑烯炔为原料，通过金属镍催化，在手性配体调控下，来高效构建手性4‑位偕二氟烯基取代吡咯烷酮的方法；即在加热条件下首先芳基硼酸与1,6‑烯炔的环化脱氟反应，以镍源为催化剂，在手性配体调控下得到手性4‑位偕二氟烯基取代吡咯烷酮。本申请方法使用了一种新颖芳基化环化脱氟串联的方法学，与之前的合成方法相比，原料商业可得、步骤简洁高效并且易于进一步衍生化，操作简单，适用于大量手性类似物的合成。
Description
技术领域
本申请涉及有机合成的技术领域，尤其涉及一种合成手性4-位偕二氟烯基取代吡咯烷酮的方法。
背景技术
吡咯烷酮骨架结构广泛存在于具有生物活性的天然产物中，同时也是合成具有药用价值的化合物的重要前体，偕二氟烯烃在位阻和电性方面类似于羰基，同时又具有更高的代谢稳定性，偕二氟烯烃基团的引入能够显著影响有机分子的理化性质和生物活性，被广泛应用于医药开发中，因此发展合成手性偕二氟烯烃取代吡咯烷酮方法学具有重要的意义。
然而，目前合成手性偕二氟烯烃取代吡咯烷酮的方法步骤冗长，底物上复杂的结构需要预先构建并保护，反应条件苛刻，不仅给环境带来污染也增加了生产成本。本发明提出了硼酸、三氟甲基烯烃取·代的1,6-烯炔为原料，通过金属镍催化，在手性配体调控下，一步高效构建手性4-位偕二氟烯基取代吡咯烷酮酮结构。
发明内容
有鉴于此，本申请提供一种合成手性4-位偕二氟烯基取代吡咯烷酮的方法，该方法简单，高效，快捷，高选择性。
本申请提供一种合成手性4-位偕二氟烯基取代吡咯烷酮的方法具体为，将 1,6-烯炔A、芳基硼酸B，在手性二茂铁骨架配体((S,Sp)-iPr-Phosferrox)调控下，以四水合醋酸镍为催化剂，在有机溶剂中加热，反应得到烯炔芳基化环化脱氟串联产物中间体C；
所述1,6-烯炔A的结构式为：
其中R1选自甲基(Me)、乙基(Et)， R2选自苯基(-Ph)、苄基(-Bn)、对甲基苯磺酰基(-Ts)；
芳基硼酸B的结构式为：
所述手性二茂铁骨架(S,Sp)-iPr-Phosferrox配体的结构式为：
所述烯炔芳基化环化脱氟串联产物中间体C：
应当理解的是，本申请的反应路线如下，
可选地，所述1,6-烯炔A的结构式为
可选地，所述芳基硼酸B的结构式为，
可选地，所述反应在惰性气体的保护下进行。
可选地，镍催化剂为四水合醋酸镍。
可选地，所述有机溶剂为三氟乙醇。
可选地，所述1,6-烯炔A的浓度为1～0.1mol/L，苯硼酸B的浓度为 2～0.2mol/L，四水合醋酸镍的浓度为0.01～0.001mol/L，手性二茂铁骨架配体的浓度为0.012～0.0012mol/L。
可选地，所述加热的温度为80℃，反应的时间为30小时。
本申请提供的合成手性4-位偕二氟烯基取代吡咯烷酮的方法，以金属镍为催化剂，在手性配体(S,Sp)-iPr-Phosferrox调控下，从而制备各种手性偕二氟烯烃取代的吡咯烷酮的方法。该方法可适用于多种含不同取代基的三氟甲基烯烃取代的1,6-烯炔与苯硼酸，反应条件温和，操作简便，官能团兼容性强，底物适用性广，原料廉价易得，是一种高效、绿色、廉价合成手性4-位偕二氟烯基取代吡咯烷酮的方法。
具体实施方式
下面将结合本申请实施例，对本申请实施例中的技术方案进行清楚、完整地描述。显然，所描述的实施例仅仅是本申请一部分实施例，而不是全部的实施例。基于本申请中的实施例，本领域技术人员在没有作出创造性劳动前提下所获得的所有其他实施例，都属于本申请保护的范围。
实施例1
合成路径如下：
制备方法如下：
在氩气氛围下称取N-(4-甲基苯磺酰基)-N-(4,4,4-三氟甲基-2-烯丙基)-2-丁炔酰胺底物(0.1mmol，34.5mg)、苯硼酸底物(0.2mmol，24.4mg)、催化剂四水合乙酸镍(2.5mg，0.01mmol，10mol％)和二茂铁骨架的 (S,Sp)-iPr-Phosferrox手性配体(5.8mg，0.012mmol，12mol％)，置于带有搅拌子的10mL封管中，加入溶剂三氟乙醇(2.0mL)。密封后加热至80℃反应30 小时。TLC监测反应结束后，反应混合物浓缩，随后通过硅胶柱层析分离(石油醚/乙酸乙酯＝50/1-5/1)，得到目标化合物(31.5mg,产率为78％)，白色固体。1H NMR(600MHz,CDCl3)δ7.98(d,J＝8.3Hz,2H),7.39-7.33(m,4H),7.32-7.28 (m,1H),7.07(d,J＝8.3Hz,2H),3.97-3.89(m,2H),3.68-3.62(m,1H),3.54(dd,J ＝9.9,3.3Hz,1H),2.47(d,J＝1.5Hz,3H),2.46(s,3H)；
13C NMR(151MHz,CDCl3)δ165.8,156.2(t,J＝289.9Hz),155.1,145.2,141.7,135.1,129.7,128.6,128.3,128.2,126.4,126.1,80.2(dd,J＝24.0,18.7Hz),49.9, 31.3(d,J＝5.6Hz),21.7,21.1；
19F NMR(565MHz,CDCl3)δ-88.1(d,J＝39.1Hz),-88.4(dd,J＝39.1,23.7Hz)HRMS:(ESI)calcd for C21H20F2NO3S+[M+H]+404.1127；found 404.1126.
HPLC conditions:AD-H column,30℃,n-Hexane/i-Propanol＝85/15as eluent,254 nm,1mL/min.tR＝6.3min(major),7.0min(minor)。
Optical Rotation:[α]D 2880.8(c 5.0,iPrOH)for 98％ee。
实施例2
合成路径如下：
制备方法如下：
在氩气氛围下称取N-苄基-N-(4,4,4-三氟甲基-2-烯丙基)-2-丁炔酰胺底物(0.1mmol，28.1mg)、苯硼酸底物(0.2mmol，24.4mg)、催化剂四水合乙酸镍(2.5mg，0.01mmol，10mol％)和二茂铁骨架的(S,Sp)-iPr-Phosferrox手性配体(5.8mg，0.012mmol，12mol％)，置于带有搅拌子的10mL封管中，加入溶剂三氟乙醇(2.0mL)。密封后加热至80℃反应30小时。TLC监测反应结束后，反应混合物浓缩，随后通过硅胶柱层析分离(石油醚/乙酸乙酯＝50/1-5/1)，得到目标化合物(21.1mg,产率为62％)，无色油状物。
1H NMR(400MHz,CDCl3)δ7.37–7.26(m,8H),7.13(d,J＝7.9Hz,2H),4.60– 4.48(m,2H),3.90(ddd,J＝23.9,10.4,2.3Hz,1H),3.58(t,J＝9.7Hz,1H),3.42(t, J＝9.0Hz,1H),2.85(dd,J＝9.9,3.0Hz,1H),2.60(s,3H).
13C NMR(101MHz,CDCl3)δ168.2,156.2(t,J＝290.0),148.8,142.9,136.4,128.9,128.5,128.4,127.8,127.6,126.6,81.2(dd,J＝22.6,18.8Hz),50.2,47.0, 31.0(d,J＝5.5Hz),20.5.
19F NMR(376MHz,CDCl3)δ-89.61(d,J＝42.7Hz),-90.15(dd,J＝48.0,23.9 Hz).
HRMS:(ESI)calcd for C21H20F2NO+[M+H]+340.1507found 340.1501.
HPLC conditions:OD-H column,30℃,n-Hexane/i-Propanol＝95/5as eluent,254 nm,1mL/min.tR＝12.0min(major),12.8min(minor)。
Optical Rotation:[α]D 2891.5(c 5.0,iPrOH)for 98％ee。
实施例3
合成路线如下：
制备方法如下：
在氩气氛围下称取N-苯基-N-(4,4,4-三氟甲基-2-烯丙基)-2-丁炔酰胺底物(0.1mmol，26.7mg)、苯硼酸底物(0.2mmol，24.4mg)、催化剂四水合乙酸镍(2.5mg，0.01mmol，10mol％)和二茂铁骨架的(S,Sp)-iPr-Phosferrox手性配体(5.8mg，0.012mmol，12mol％)，置于带有搅拌子的10mL封管中，加入溶剂三氟乙醇(2.0mL)。密封后加热至80℃反应30小时。TLC监测反应结束后，反应混合物浓缩，随后通过硅胶柱层析分离(石油醚/乙酸乙酯＝50/1-5/1)，得到目标化合物(18.5mg,产率为57％)，白色固体。
1H NMR(600MHz,CDCl3)δ7.68-7.64(m,2H),7.44-7.36(m,4H),7.34-7.29(m, 1H),7.17(tt,J＝8.4,1.3Hz,3H),4.12(ddd,J＝24.0,10.3,2.3Hz,1H),4.02(ddd, J＝9.3,7.8,1.2Hz,1H),3.76-3.70(m,1H),3.44(ddd,J＝9.6,3.0,0.9Hz,1H), 2.62(d,J＝1.5Hz,3H)；
13C NMR(151MHz,CDCl3)δ167.2,156.2(t,J＝289.2Hz),150.1,142.7,139.5,128.9,128.8,128.5,127.7,126.5,124.7,119.8,81.1(dd,J＝23.2,18.7Hz),51.8(t, J＝3.0Hz),31.1(d,J＝5.3Hz),20.6；
19F NMR(565MHz,CDCl3)δ-89.1(d,J＝42.3Hz),-89.5(dd,J＝41.8,24.2Hz)；HRMS:(ESI)calcd for C20H18F2NO+[M+H]+326.1351；found 326.1345.
HPLC conditions:AD-H column,30℃,n-Hexane/i-Propanol＝90/10as eluent,254 nm,1mL/min.tR＝6.2min(major),8.2min(minor)。
Optical Rotation:[α]D 2841.9(c 3.0,iPrOH)for 97％ee。
实施例4
合成路径如下：
制备方法如下：
在氩气氛围下称取N-环丙基-N-(4,4,4-三氟甲基-2-烯丙基)-2-丁炔酰胺底物(0.1mmol，23.1mg)、苯硼酸底物(0.2mmol，24.4mg)、催化剂四水合乙酸镍(2.5mg，0.01mmol，10mol％)和二茂铁骨架的(S,Sp)-iPr-Phosferrox手性配体(5.8mg，0.012mmol，12mol％)，置于带有搅拌子的10mL封管中，加入溶剂三氟乙醇(2.0mL)。密封后加热至80℃反应30小时。TLC监测反应结束后，反应混合物浓缩，随后通过硅胶柱层析分离(石油醚/乙酸乙酯＝50/1-5/1)，得到目标化合物(16.5mg,产率为57％)，白色固体。
1H NMR(400MHz,CDCl3)δ7.37–7.33(m,2H),7.31–7.27(m,1H),7.13–7.11 (m,2H),3.94(ddd,J＝23.9,10.3,2.6Hz,1H),3.56(t,J＝9.5Hz,1H),3.54–3.40 (m,1H),2.89(dd,J＝9.7,2.9Hz,1H),2.78-2.72(m,1H),2.56(s,3H),0.86–0.66 (m,4H).
13C NMR(101MHz,CDCl3)δ169.8,159.1,148.4,142.9,129.0,128.5,127.5,126.6,81.2(dd,J＝22.9,18.8Hz),51.01,31.3(d,J＝5.2Hz),25.8,20.4,5.2,4.9.
19F NMR(376MHz,CDCl3)δ-89.63(d,J＝43.0Hz),-90.07(dd,J＝42.7,24.2 Hz).
HRMS:(ESI)calcd for C17H18F2NO+[M+H]+290.1351found 290.1346
HPLC conditions:AD-H column,30℃,n-Hexane/i-Propanol＝92/8as eluent,254 nm,1mL/min.tR＝5.7min(major),5.9min(minor)。
Optical Rotation:[α]D 2829.9(c 3.0,iPrOH)for 98％ee。
实施例5
合成路径如下：
制备方法如下：
在氩气氛围下称取N-苄基-N-(4,4,4-三氟甲基-2-烯丙基)-5-(苄氧基)-戊-2-炔酰胺底物(0.1mmol，40.1mg)、苯硼酸底物(0.2mmol，24.4mg)、催化剂四水合乙酸镍(2.5mg，0.01mmol，10mol％)和二茂铁骨架的(S,Sp)-iPr-Phosferrox 手性配体(5.8mg，0.012mmol，12mol％)，置于带有搅拌子的10mL封管中，加入溶剂三氟乙醇(2.0mL)。密封后加热至80℃反应30小时。TLC监测反应结束后，反应混合物浓缩，随后通过硅胶柱层析分离(石油醚/乙酸乙酯＝ 50/1-5/1)，得到目标化合物(28.6mg,产率为62％)，无色油状物。
1H NMR(400MHz,CDCl3)δ7.36–7.25(m,13H),7.12(d,J＝7.3Hz,2H),4.61– 4.42(m,4H),4.02–3.84(m,2H),3.59-3.52(m,3H),3.42(t,J＝8.9Hz,1H), 3.13-3.08(m,1H),2.85(dd,J＝9.9,2.9Hz,1H).
13C NMR(101MHz,CDCl3)δ167.6,156.3(t,J＝290.0),149.9,140.9,138.8,136.4,130.1,128.9,128.45,128.40,128.3,127.8,127.7,127.6,127.4,127.3,110.9,81.00(dd,J＝22.9,19.0Hz),72.4,68.5,50.2,47.0,32.8,31.1(d,J＝5.4Hz).
19F NMR(376MHz,CDCl3)δ-89.51(d,J＝42.0Hz),-90.16(dd,J＝42.1,24.1 Hz).
HRMS:(ESI)calcd for C29H28F2NO2 +[M+H]+460.2083found 460.2081.
HPLC conditions:AD-H column,30℃,n-Hexane/i-Propanol＝90/10as eluent,254 nm,1.0
mL/min.tR＝8.6min(minor),9.4min(major)。
Optical Rotation:[α]D 2814.9(c 3.0,iPrOH)for 99％ee。
实施例6
合成路径如下：
制备方法如下：
在氩气氛围下称取N-苄基-N-(4,4,4-三氟甲基-2-烯丙基)-5-(N,N-二苄基)-戊-2-炔酰胺底物(0.1mmol，49mg)、苯硼酸底物(0.2mmol，24.4mg)、催化剂四水合乙酸镍(2.5mg，0.01mmol，10mol％)和二茂铁骨架的 (S,Sp)-iPr-Phosferrox手性配体(5.8mg，0.012mmol，12mol％)，置于带有搅拌子的10mL封管中，加入溶剂三氟乙醇(2.0mL)。密封后加热至80℃反应30 小时。TLC监测反应结束后，反应混合物浓缩，随后通过硅胶柱层析分离(石油醚/乙酸乙酯＝50/1-5/1)，得到目标化合物(32.4mg,产率为59％)，淡黄色固体。
1H NMR(400MHz,CDCl3)δ7.35–7.16(m,18H),6.94(dd,J＝6.6,2.9Hz,2H), 4.54(d,J＝14.7Hz,1H),4.42(d,J＝14.6Hz,1H),3.92–3.80(m,2H),3.67– 3.476(m,5H),3.42–3.36(m,1H),3.08(ddd,J＝13.2,8.5,5.8Hz,1H),2.81(dd,J ＝9.8,2.8Hz,1H),2.69–2.49(m,2H).
13C NMR(101MHz,CDCl3)δ167.7,156.2(dd,J＝289.4,286.8Hz)，151.5,141.0,139.8,136.4,129.2,128.9,128.3,128.2,128.1,127.7,127.4,127.1,126.7,81.2(dd, J＝23.1,18.9Hz),57.5,51.6,50.2,46.9,31.0(d,J＝5.3Hz),29.4.
19F NMR(376MHz,CDCl3)δ-89.70(d,J＝42.7Hz),-90.21(dd,J＝42.0,23.8 Hz).
HRMS:(ESI)calcd for C36H35F2N2O+[M+H]+549.2712found 549.2705.
HPLC conditions:AD-H column,30℃,n-Hexane/i-Propanol＝85/15as eluent,254 nm,1.0
mL/min.tR＝6.6min(minor),8.6min(major)。
Optical Rotation:[α]D 2813.3(c 3.0,iPrOH)for 97％ee。
实施例7
合成路径如下：
制备方法如下：
在氩气氛围下称取N-苄基-N-(4,4,4-三氟甲基-2-烯丙基)-5-(甲酸乙酯)-戊-2-炔酰胺底物(0.1mmol，36.7mg)、苯硼酸底物(0.2mmol，24.4mg)、催化剂四水合乙酸镍(2.5mg，0.01mmol，10mol％)和二茂铁骨架的 (S,Sp)-iPr-Phosferrox手性配体(5.8mg，0.012mmol，12mol％)，置于带有搅拌子的10mL封管中，加入溶剂三氟乙醇(2.0mL)。密封后加热至80℃反应30 小时。TLC监测反应结束后，反应混合物浓缩，随后通过硅胶柱层析分离(石油醚/乙酸乙酯＝50/1-5/1)，得到目标化合物(25.8mg,产率为60％)，淡黄色油状物。
1H NMR(400MHz,CDCl3)δ7.38–7.24(m,8H),7.12–7.06(m,2H),4.58(d,J＝14.5Hz,1H),4.46(d,J＝14.6Hz,1H),4.04–3.81(m,4H),3.57-3.50(m,1H), 3.46-3.40(m,1H),3.07-2.99(m,1H),2.89–2.82(m,1H),2.48–2.30(m,2H),1.17 (t,J＝7.2Hz,3H).
13C NMR(101MHz,CDCl3)δ172.9,167.5,156.3(dd,J＝289.4,286.8Hz),150.9,140.3,136.3,129.6,128.9,128.5,128.4,127.8,127.3,80.9(dd,J＝23.1,18.9Hz).60.4,50.2,47.0,32.9,31.06(d,J＝5.3Hz),28.2,14.2.
19F NMR(376MHz,CDCl3)δ-89.32(d,J＝42.3Hz),-90.08(dd,J＝41.7,23.8 Hz).
HRMS:(ESI)calcd for C25H26F2NO3 +[M+H]+426.1875found 426.1865.
HPLC conditions:AS-H column,30℃,n-Hexane/i-Propanol＝95/5as eluent,254 nm,1.0
mL/min.tR＝8.3min(minor),9.6min(major)。
Optical Rotation:[α]D 2825.3(c 4.0,iPrOH)for 98％ee。
实施例8
合成路径如下：
制备方法如下：
在氩气氛围下称取N-(4-甲基苯磺酰基)-N-(4,4,4-三氟甲基-2-烯丙基)-2-丁炔酰胺底物(0.1mmol，34.5mg)、4-三氟甲氧基苯硼酸底物(0.2mmol，41.2mg)、催化剂四水合乙酸镍(2.5mg，0.01mmol，10mol％)和二茂铁骨架的 (S,Sp)-iPr-Phosferrox手性配体(5.8mg，0.012mmol，12mol％)，置于带有搅拌子的10mL封管中，加入溶剂三氟乙醇(2.0mL)。密封后加热至80℃反应30 小时。TLC监测反应结束后，反应混合物浓缩，随后通过硅胶柱层析分离(石油醚/乙酸乙酯＝50/1-5/1)，得到目标化合物(32.6mg,产率为67％)，白色固体。1H NMR(600MHz,CDCl3)δ8.00-7.95(m,2H),7.40-7.35(m,2H),7.23-7.19(m, 2H),7.13-7.08(m,2H),3.99-3.87(m,2H),3.67-3.59(m,1H),3.54(m,1H),2.46(s, 3H),2.45(s,3H)；
13C NMR(151MHz,CDCl3)δ165.5,156.7(t,J＝289.9Hz),153.4,148.8,145.3,140.3,135.0,129.7,128.3,127.8,127.3,121.2,120.4(q,J＝193.3Hz),79.9(dd,J ＝24.2,18.8Hz),49.7,31.2(d,J＝5.5Hz),21.7,21.0；
19F NMR(565MHz,CDCl3)δ-58.0,-87.8(d,J＝39.3Hz),-88.5(dd,J＝39.1,23.5Hz)；
HRMS:(ESI)calcd for C22H19F5NO4S+[M+H]+488.0950；found 488.0947.
HPLC conditions:AD-H column,30℃,n-Hexane/i-Propanol＝90/10as eluent,254 nm,0.5mL/min.tR＝14.5min(major),15.0min(minor)。
Optical Rotation:[α]D 2810.2(c 6.0,iPrOH)for 96％ee。
实施例9
合成路径如下：
制备方法如下：
在氩气氛围下称取N-(4-甲基苯磺酰基)-N-(4,4,4-三氟甲基-2-烯丙基)-2-丁炔酰胺底物(0.1mmol，34.5mg)、4-醛基苯硼酸底物(0.2mmol，30mg)、催化剂四水合乙酸镍(2.5mg，0.01mmol，10mol％)和二茂铁骨架的 (S,Sp)-iPr-Phosferrox手性配体(5.8mg，0.012mmol，12mol％)，置于带有搅拌子的10mL封管中，加入溶剂三氟乙醇(2.0mL)。密封后加热至80℃反应30 小时。TLC监测反应结束后，反应混合物浓缩，随后通过硅胶柱层析分离(石油醚/乙酸乙酯＝50/1-5/1)，得到目标化合物(31.1mg,产率为72％)，白色固体。
1H NMR(600MHz,CDCl3)δ10.02(s,1H),8.02-7.95(m,2H),7.93-7.86(m,2H),7.40-7.36(m,2H),7.26-7.23(m,2H),4.02-3.88(m,2H),3.66-3.50(m,2H),2.48(d, J＝1.6Hz,3H),2.47(s,3H)；
13C NMR(151MHz,CDCl3)δ191.4,165.4,156.2(t,J＝289.9Hz),153.2,147.7,145.4,135.8,135.0,130.1,129.8,128.3,127.4,126.9,80.0(dd,J＝24.3,18.7Hz), 49.8(t,J＝3.3Hz),31.1(d,J＝5.6Hz),21.7,20.8；
19F NMR(565MHz,CDCl3)δ-87.4(d,J＝37.7Hz),-88.0(dd,J＝38.2,23.3Hz)；HRMS:(ESI)calcd for C22H20F2NO4S+[M+H]+432.1076；found 432.1076.
HPLC conditions:AD-H column,30℃,n-Hexane/i-Propanol＝85/15as eluent,254 nm,1mL/min.tR＝14.8min(major),15.7min(minor)。
Optical Rotation:[α]D 2758.2(c 2.0,iPrOH)for 94％ee。
实施例10
合成路径如下：
制备方法如下：
在氩气氛围下称取N-(4-甲基苯磺酰基)-N-(4,4,4-三氟甲基-2-烯丙基)-2-丁炔酰胺底物(0.1mmol，34.5mg)、4-氰基苯硼酸底物(0.2mmol，29.4mg)、催化剂四水合乙酸镍(2.5mg，0.01mmol，10mol％)和二茂铁骨架的 (S,Sp)-iPr-Phosferrox手性配体(5.8mg，0.012mmol，12mol％)，置于带有搅拌子的10mL封管中，加入溶剂三氟乙醇(2.0mL)。密封后加热至80℃反应30 小时。TLC监测反应结束后，反应混合物浓缩，随后通过硅胶柱层析分离(石油醚/乙酸乙酯＝50/1-5/1)，得到目标化合物(26.1mg,产率为61％)，白色固体。1H NMR(600MHz,CDCl3)δ8.00-7.94(m,2H),7.69-7.64(m,2H),7.41-7.35(m, 2H),7.21-7.16(m,2H),3.96(tt,J＝10.0,1.5Hz,2H),3.62-3.50(m,2H),2.51-2.41 (m,6H)；13C NMR(151MHz,CDCl3)δ165.2,156.2(t,J＝290.2Hz),152.3,146.2, 145.5,134.9,132.5,129.8,128.3,127.1,118.2,112.1,79.9(dd,J＝24.2,18.7Hz), 49.7,31.1(d,J＝5.6Hz),21.7,20.7；19FNMR(565MHz,CDCl3)δ-87.3(d,J＝ 37.5Hz),-88.0(dd,J＝37.6,23.7Hz)；
HRMS:(ESI)calcd for C22H19F2N2O3S+[M+H]+429.1079；found 429.1080；
HPLC conditions:AD-H column,30℃,n-Hexane/i-Propanol＝85/15as eluent,254 nm,1mL/min.tR＝14.0min(major),14.9min(minor)。
Optical Rotation:[α]D 2838.5(c 2.0,iPrOH)for 96％ee。
实施例11
合成路径如下：
制备方法如下：
在氩气氛围下称取N-(4-甲基苯磺酰基)-N-(4,4,4-三氟甲基-2-烯丙基)-2-丁炔酰胺底物(0.1mmol，34.5mg)、4-甲酸乙酯苯硼酸底物(0.2mmol，38.8mg)、催化剂四水合乙酸镍(2.5mg，0.01mmol，10mol％)和二茂铁骨架的 (S,Sp)-iPr-Phosferrox手性配体(5.8mg，0.012mmol，12mol％)，置于带有搅拌子的10mL封管中，加入溶剂三氟乙醇(2.0mL)。密封后加热至80℃反应30 小时。TLC监测反应结束后，反应混合物浓缩，随后通过硅胶柱层析分离(石油醚/乙酸乙酯＝50/1-5/1)，得到目标化合物(32.2mg,产率为70％)，白色固体。
1H NMR(600MHz,CDCl3)δ8.07-8.01(m,2H),8.01-7.95(m,2H),7.41-7.35(m, 2H),7.17-7.10(m,2H),4.38(q,J＝7.2Hz,2H),4.07-3.86(m,2H),3.66-3.49(m, 2H),2.46(m,6H),1.40(t,J＝7.1Hz,3H)；
13C NMR(151MHz,CDCl3)δ165.9,165.5,156.2(t,J＝289.9Hz),153.7,146.1,145.3,135.0,130.2,129.9,129.7,128.3,127.2,126.2,80.1(dd,J＝24.1,18.7Hz),61.2,49.9(d,J＝3.2Hz),31.2(d,J＝5.6Hz),21.7,20.9,14.3；
19F NMR(565MHz,CDCl3)δ-87.5(d,J＝38.3Hz),-87.8(dd,J＝38.1,23.4Hz)；HRMS:(ESI)calcd for C24H24F2NO5S+[M+H]+476.1338；found 476.1337；
HPLC conditions:AD-H column,30℃,n-Hexane/i-Propanol＝85/15as eluent,254 nm,1mL/min.tR＝10.4min(minor),12.7min(major)。
Optical Rotation:[α]D 2828.9(c 8.0,iPrOH)for 93％ee。
实施例12
合成路径如下：
制备方法如下：
在氩气氛围下称取N-(4-甲基苯磺酰基)-N-(4,4,4-三氟甲基-2-烯丙基)-2-丁炔酰胺底物(0.1mmol，34.5mg)、4-醛基苯硼酸底物(0.2mmol，38.6mg)、催化剂四水合乙酸镍(2.5mg，0.01mmol，10mol％)和二茂铁骨架的 (S,Sp)-iPr-Phosferrox手性配体(5.8mg，0.012mmol，12mol％)，置于带有搅拌子的10mL封管中，加入溶剂三氟乙醇(2.0mL)。密封后加热至80℃反应30 小时。TLC监测反应结束后，反应混合物浓缩，随后通过硅胶柱层析分离(石油醚/乙酸乙酯＝50/1-5/1)，得到目标化合物(31.8mg,产率为67％)，白色固体。
1H NMR(600MHz,CDCl3)δ8.01-7.94(m,2H),7.44-7.39(m,2H),7.37(m,2H), 7.13-7.08(m,2H),4.01-3.92(m,2H),3.70-3.63(m,1H),3.55(dd,J＝10.0,3.4Hz, 1H),3.11(s,3H),2.95(s,3H),2.50-2.42(m,6H)；
13C NMR(151MHz,CDCl3)δ170.8,165.6,156.2(t,J＝289.9Hz),154.2,145.3,142.9,136.3,135.0,129.7,128.3,127.4,126.9,126.2,80.2(dd,J＝23.9,18.6Hz), 49.7(t,J＝3.2Hz),39.2,35.3,31.2(d,J＝5.5Hz),21.7,21.0；
19F NMR(565MHz,CDCl3)δ-88.0(d,J＝39.0Hz),-88.6(dd,J＝38.5,24.0Hz)；HRMS:(ESI)calcd for C24H25F2N2O4S+[M+H]+475.1498；
HPLC conditions:OD-H column,30℃,n-Hexane/i-Propanol＝85/15as eluent,254 nm,1mL/min.tR＝37.9min(major),44.5min(minor)。
Optical Rotation:[α]D 2833.6(c 8.0,iPrOH)for 98％ee。
实施例13
合成路径如下：
制备方法如下：
在氩气氛围下称取N-(4-甲基苯磺酰基)-N-(4,4,4-三氟甲基-2-烯丙基)-2-丁炔酰胺底物(0.1mmol，34.5mg)、4-甲磺酰基苯硼酸底物(0.2mmol，40mg)、催化剂四水合乙酸镍(2.5mg，0.01mmol，10mol％)和二茂铁骨架的 (S,Sp)-iPr-Phosferrox手性配体(5.8mg，0.012mmol，12mol％)，置于带有搅拌子的10mL封管中，加入溶剂三氟乙醇(2.0mL)。密封后加热至80℃反应30 小时。TLC监测反应结束后，反应混合物浓缩，随后通过硅胶柱层析分离(石油醚/乙酸乙酯＝50/1-5/1)，得到目标化合物(29.81mg,产率为62％)，白色固体。
1H NMR(600MHz,CDCl3)δ8.01-7.97(m,2H),7.97-7.94(m,2H),7.41-7.35(m, 2H),7.31-7.26(m,2H),4.01-3.88(m,2H),3.63-3.52(m,2H),3.03(s,3H), 2.52-2.41(m,6H)；
13C NMR(151MHz,CDCl3)δ165.2,156.2(t,J＝290.0Hz),152.5,147.2,145.5,140.2,134.9,130.0,129.8,128.3,127.9,127.3,79.9(dd,J＝24.3,18.7Hz),49.6, 44.5,31.1(d,J＝5.6Hz),21.7,20.7；
19F NMR(565MHz,CDCl3)δ-87.5(d,J＝37.8Hz),-88.4(dd,J＝37.8,23.7Hz)；HRMS:(ESI)calcd for C22H22F2NO5S2 +[M+H]+482.0902；found 482.0904.
HPLC conditions:OD-H column,30℃,n-Hexane/i-Propanol＝70/30as eluent,254 nm,1mL/min.tR＝21.0min(major),25.8min(minor).
Optical Rotation:[α]D 281.1(c 8.0,iPrOH)for 99％ee.
实施例14
合成路径如下：
制备方法如下：
在氩气氛围下称取N-(4-甲基苯磺酰基)-N-(4,4,4-三氟甲基-2-烯丙基)-2-丁炔酰胺底物(0.1mmol，34.5mg)、二苯并呋喃-2-硼酸底物(0.2mmol，42.4mg)、催化剂四水合乙酸镍(2.5mg，0.01mmol，10mol％)和二茂铁骨架的 (S,Sp)-iPr-Phosferrox手性配体(5.8mg，0.012mmol，12mol％)，置于带有搅拌子的10mL封管中，加入溶剂三氟乙醇(2.0mL)。密封后加热至80℃反应30 小时。TLC监测反应结束后，反应混合物浓缩，随后通过硅胶柱层析分离(石油醚/乙酸乙酯＝50/1-5/1)，得到目标化合物(25.7mg,产率为52％)，白色固体。
1H NMR(600MHz,CDCl3)δ8.04-7.96(m,2H),7.91(ddd,J＝7.7,1.3,0.7Hz, 1H),7.68(dd,J＝1.9,0.6Hz,1H),7.58(dt,J＝8.2,0.9Hz,1H),7.55(dd,J＝8.4, 0.6Hz,1H),7.49(ddd,J＝8.4,7.3,1.3Hz,1H),7.42-7.38(m,2H),7.38-7.33(m, 1H),7.18(dd,J＝8.5,1.9Hz,1H),4.02(ddd,J＝23.2,10.3,2.6Hz,1H),3.96(ddd, J＝9.9,7.9,1.2Hz,1H),3.72(s,1H),3.58(ddd,J＝10.0,3.3,0.9Hz,1H),2.57(d, J＝1.5Hz,3H),2.48(s,3H)；
13C NMR(151MHz,CDCl3)δ165.8,156.6,156.2(d,J＝289.9Hz),155.7,154.9,145.2,136.5,135.2,129.7,128.3,127.7,126.9,125.4,124.5,123.6,123.0,120.6,118.5,111.9,111.8,80.4(dd,J＝23.6,18.8Hz),50.0(t,J＝3.1Hz),31.7(d,J＝5.4 Hz),21.7,21.6；
19F NMR(565MHz,CDCl3)δ-87.8(d,J＝38.2Hz),-88.0(dd,J＝38.9,23.4Hz)；HRMS:(ESI)calcd for C27H22F2NO4S+[M+H]+494.1232；found 494.1232；
HPLC conditions:AD-H column,30℃,n-Hexane/i-Propanol＝90/10as eluent,254 nm,1mL/min.tR＝14.1min(major),14.9min(minor)。
Optical Rotation:[α]D 2864.0(c 8.0,iPrOH)for 97％ee。
以上所述，仅为本申请较佳的具体实施方式，但本申请的保护范围并不局限于此，任何熟悉本技术领域的技术人员在本申请揭露的技术范围内，可轻易想到的变化或替换，都应涵盖在本申请的保护范围之内。
Claims (8)
1.一种合成手性4-位偕二氟烯基取代吡咯烷酮的方法，其特征在于，具体为，将1,6-烯炔A、芳基硼酸B，在手性二茂铁骨架配体((S,Sp)-iPr-Phosferrox)调控下，以镍源为催化剂，在有机溶剂中加热，反应得到烯炔芳基化环化脱氟串联产物中间体C；
所述1,6-烯炔A的结构式为：
其中R1选自甲基(Me)、乙基(Et)，R2选自苯基(-Ph)、苄基(-Bn)、对甲基苯磺酰基(-Ts)；
芳基硼酸B的结构式为：
所述手性二茂铁骨架(S,Sp)-iPr-Phosferrox配体的结构式为：
所述烯炔芳基化环化脱氟串联产物中间体C：
2.根据权利要求1所述方法，其特征在于，所述1,6-烯炔A的结构式为
3.根据权利要求1所述方法，其特征在于，所述芳基硼酸B的结构式为，
4.根据权利要求1所述方法，其特征在于，所述反应在惰性气体的保护下进行。
5.根据权利要求1所述方法，其特征在于，所述镍源为四水合醋酸镍。
6.根据权利要求1所述方法，其特征在于，所述有机溶剂为三氟乙醇。
7.根据权利要求5所述的方法，其特征在于，所述1,6-烯炔A的浓度为1～0.1mol/L，苯硼酸B的浓度为2～0.2mol/L，四水合醋酸镍的浓度为0.01～0.001mol/L，手性二茂铁骨架(S,Sp)-iPr-Phosferrox配体的浓度为0.012～0.0012mol/L。
8.根据权利要求1所述方法，其特征在于，所述加热的温度为80℃，反应的时间为30小时。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211162260.XA CN115490627A (zh) | 2022-09-23 | 2022-09-23 | 一种合成手性4-位偕二氟烯基取代吡咯烷酮的方法 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211162260.XA CN115490627A (zh) | 2022-09-23 | 2022-09-23 | 一种合成手性4-位偕二氟烯基取代吡咯烷酮的方法 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN115490627A true CN115490627A (zh) | 2022-12-20 |
Family
ID=84469492
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202211162260.XA Withdrawn CN115490627A (zh) | 2022-09-23 | 2022-09-23 | 一种合成手性4-位偕二氟烯基取代吡咯烷酮的方法 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115490627A (zh) |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106966948A (zh) * | 2017-02-21 | 2017-07-21 | 安阳师范学院 | 一种偕二氟取代吡咯烷酮化合物的合成方法 |
| CN110078605A (zh) * | 2019-05-29 | 2019-08-02 | 河南师范大学 | 有机硼酸与α,β-不饱和酮的不对称共轭加成反应合成光学活性三氟甲基化合物的方法 |
| CN113527177A (zh) * | 2021-08-31 | 2021-10-22 | 南京林业大学 | 一种2-氰基吲哚取代的偕二氟烯烃化合物及其制备方法和应用 |
| CN114057785A (zh) * | 2021-12-13 | 2022-02-18 | 河南师范大学 | 手性α-二氟甲基硅烷化合物的合成方法 |
| CN114716361A (zh) * | 2020-12-22 | 2022-07-08 | 武汉大学 | 一种合成手性螺环茚酮-吡咯类化合物的方法 |
-
2022
- 2022-09-23 CN CN202211162260.XA patent/CN115490627A/zh not_active Withdrawn
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106966948A (zh) * | 2017-02-21 | 2017-07-21 | 安阳师范学院 | 一种偕二氟取代吡咯烷酮化合物的合成方法 |
| CN110078605A (zh) * | 2019-05-29 | 2019-08-02 | 河南师范大学 | 有机硼酸与α,β-不饱和酮的不对称共轭加成反应合成光学活性三氟甲基化合物的方法 |
| CN114716361A (zh) * | 2020-12-22 | 2022-07-08 | 武汉大学 | 一种合成手性螺环茚酮-吡咯类化合物的方法 |
| CN113527177A (zh) * | 2021-08-31 | 2021-10-22 | 南京林业大学 | 一种2-氰基吲哚取代的偕二氟烯烃化合物及其制备方法和应用 |
| CN114057785A (zh) * | 2021-12-13 | 2022-02-18 | 河南师范大学 | 手性α-二氟甲基硅烷化合物的合成方法 |
Non-Patent Citations (1)
| Title |
|---|
| DR. KUAI WANG，等: "Nickel-Catalyzed Defluorinative Asymmetric Cyclization of Fluoroalkyl-Substituted 1, 6-Enynes for the Synthesis of Seletracetam", 《ANGEWANDTE CHEMIE INTERNATIONAL EDITION》, vol. 61, no. 46, pages 202212664 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Sakai et al. | Rhodium‐catalyzed addition of organoboronic acids to aldehydes | |
| Takenaka et al. | NCN pincer palladium complexes: Their preparation via a ligand introduction route and their catalytic properties | |
| Arita et al. | Synthesis and Reactivities of Cp* Ir Amide and Hydride Complexes Bearing C− N Chelate Ligands | |
| Hao et al. | A cationic NCN pincer Platinum (II) aquo complex with a bis (imidazolinyl) phenyl ligand: Studies toward its synthesis and asymmetric Friedel–Crafts alkylation of indoles with nitroalkenes | |
| Wallner et al. | Synthesis of new chiral pincer-complex catalysts for asymmetric allylation of sulfonimines | |
| Wang et al. | Synthesis of novel N, P chiral ligands for palladium-catalyzed asymmetric allylations: the effect of binaphthyl backbone on the enantioselectivity | |
| Yamago et al. | Tertiary phosphines, P-chiral phosphinites and phosphonic acid esters bearing fullerene substituent. Metal complexes and redox properties | |
| Chapman et al. | Enantioselective rhodium-catalysed addition of boronic acids using C2-symmetric aryl diphosphite ligands | |
| Imamoto et al. | Optically active 1, 1′-di-tert-butyl-2, 2′-diphosphetanyl and its application in rhodium-catalyzed asymmetric hydrogenations | |
| Nieto et al. | Functionalization of methyl (R)-phenylglycinate through orthopalladation: C− hal, C− O, C− N, and C− C bond coupling | |
| Coqueret et al. | Platinum-catalyzed hydrosilylation of allyl aryl ethers: kinetic investigation at moderately high dilution | |
| Ogasawara et al. | Kinetic resolution of planar-chiral ferrocenylphosphine derivatives by molybdenum-catalyzed asymmetric ring-closing metathesis and their application in asymmetric catalysis | |
| Wang et al. | New chiral ferrocenyl amidophosphine ligand for remarkable improvement of enantioselectivities in copper-catalyzed addition of diethylzinc to N-sulfonylimines | |
| Zeng et al. | New unsymmetrical hybrid ferrocenylphosphine-phosphoramidite ligands derived from H8-BINOL for highly efficient Rh-catalyzed enantioselective hydrogenation | |
| Sibi et al. | Enantioselective radical reactions: the use of metal triflimides as Lewis acids | |
| EP2364214A1 (en) | Method for preparation of amides from alcohols and amines by extrusion of hydrogen | |
| Zhao et al. | Regioselective C− H Activation of Toluene with a 1, 2-Bis (N-7-azaindolyl) benzene Platinum (II) Complex | |
| Han et al. | Chiral ferrocenyl P, S-ligands for highly efficient copper-catalyzed asymmetric [3+ 2] cycloaddition of azomethine ylides | |
| Galland et al. | Enantiopure 1-rH-2-c, 5-t-diphenylphospholane as ligand in Rh-catalyzed asymmetric hydrogenation | |
| CN115490627A (zh) | 一种合成手性4-位偕二氟烯基取代吡咯烷酮的方法 | |
| Boebel et al. | Conversion of 1, 3-disubstituted arenes to chiral α, α-diaryl methylammonium chlorides using arene borylation | |
| Yao et al. | [NO]-and [NN]-coordination mode rhodium complexes based on a flexible ligand: synthesis, reactivity and catalytic activity | |
| Mino et al. | Palladium-catalyzed asymmetric allylic substitution using planar chiral hydrazone ligands | |
| Bolm et al. | New chiral ligands derived from mandelic acid: Synthesis and application in the asymmetric phenyl transfer reaction to an aromatic aldehyde | |
| Mino et al. | Palladium-catalyzed asymmetric allylic alkylation using chiral hydrazone ligands with ferrocene skeleton |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WW01 | Invention patent application withdrawn after publication |
Application publication date: 20221220 |
|
| WW01 | Invention patent application withdrawn after publication |