CN115246800A - 烯基内酯类化合物及其合成制备 - Google Patents
烯基内酯类化合物及其合成制备 Download PDFInfo
- Publication number
- CN115246800A CN115246800A CN202110464424.3A CN202110464424A CN115246800A CN 115246800 A CN115246800 A CN 115246800A CN 202110464424 A CN202110464424 A CN 202110464424A CN 115246800 A CN115246800 A CN 115246800A
- Authority
- CN
- China
- Prior art keywords
- compound
- group
- alkenyl
- substituted
- reaction
- 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.)
- Pending
Links
- -1 Alkenyl lactone compound Chemical class 0.000 title claims abstract description 28
- 230000015572 biosynthetic process Effects 0.000 title claims abstract description 12
- 238000003786 synthesis reaction Methods 0.000 title claims abstract description 12
- 238000002360 preparation method Methods 0.000 title abstract description 7
- 150000001875 compounds Chemical class 0.000 claims abstract description 33
- 238000006243 chemical reaction Methods 0.000 claims abstract description 18
- 230000002194 synthesizing effect Effects 0.000 claims abstract description 8
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 18
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims description 16
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 16
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 13
- 125000003342 alkenyl group Chemical group 0.000 claims description 11
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 9
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 9
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 9
- 239000012074 organic phase Substances 0.000 claims description 9
- 238000004809 thin layer chromatography Methods 0.000 claims description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- 238000003756 stirring Methods 0.000 claims description 8
- 125000000304 alkynyl group Chemical group 0.000 claims description 7
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 7
- 238000001035 drying Methods 0.000 claims description 7
- 125000000623 heterocyclic group Chemical group 0.000 claims description 7
- 238000000034 method Methods 0.000 claims description 7
- 238000005406 washing Methods 0.000 claims description 7
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 6
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 6
- 238000004440 column chromatography Methods 0.000 claims description 6
- 229940126214 compound 3 Drugs 0.000 claims description 6
- 125000001041 indolyl group Chemical group 0.000 claims description 6
- 239000000126 substance Substances 0.000 claims description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims description 5
- JXDYKVIHCLTXOP-UHFFFAOYSA-N isatin Chemical group C1=CC=C2C(=O)C(=O)NC2=C1 JXDYKVIHCLTXOP-UHFFFAOYSA-N 0.000 claims description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
- 239000007818 Grignard reagent Substances 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 229940125904 compound 1 Drugs 0.000 claims description 4
- 229940125782 compound 2 Drugs 0.000 claims description 4
- 238000001514 detection method Methods 0.000 claims description 4
- 150000004795 grignard reagents Chemical class 0.000 claims description 4
- 230000035484 reaction time Effects 0.000 claims description 4
- 238000001308 synthesis method Methods 0.000 claims description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 3
- 125000001931 aliphatic group Chemical group 0.000 claims description 3
- 125000003118 aryl group Chemical group 0.000 claims description 3
- 238000001816 cooling Methods 0.000 claims description 3
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- 238000010438 heat treatment Methods 0.000 claims description 3
- 238000010791 quenching Methods 0.000 claims description 3
- 230000000171 quenching effect Effects 0.000 claims description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 3
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 claims description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
- 125000004185 ester group Chemical group 0.000 claims description 2
- 125000001072 heteroaryl group Chemical group 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- OTCKOJUMXQWKQG-UHFFFAOYSA-L magnesium bromide Chemical compound [Mg+2].[Br-].[Br-] OTCKOJUMXQWKQG-UHFFFAOYSA-L 0.000 claims description 2
- 229910001623 magnesium bromide Inorganic materials 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- 229910052760 oxygen Inorganic materials 0.000 claims description 2
- 239000001301 oxygen Substances 0.000 claims description 2
- 239000010703 silicon Substances 0.000 claims description 2
- 229910052710 silicon Inorganic materials 0.000 claims description 2
- 229910052717 sulfur Inorganic materials 0.000 claims description 2
- 239000011593 sulfur Substances 0.000 claims description 2
- 238000001291 vacuum drying Methods 0.000 claims description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 abstract description 25
- 229910052763 palladium Inorganic materials 0.000 abstract description 14
- 238000007363 ring formation reaction Methods 0.000 abstract description 8
- 239000003054 catalyst Substances 0.000 abstract description 7
- 150000001717 carbocyclic compounds Chemical class 0.000 abstract description 6
- 150000002391 heterocyclic compounds Chemical class 0.000 abstract description 6
- 229910052751 metal Inorganic materials 0.000 abstract description 5
- 239000002184 metal Substances 0.000 abstract description 5
- 238000005937 allylation reaction Methods 0.000 abstract description 4
- 239000002243 precursor Substances 0.000 description 7
- 238000006555 catalytic reaction Methods 0.000 description 6
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 5
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 229940125773 compound 10 Drugs 0.000 description 3
- 150000001923 cyclic compounds Chemical class 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 3
- UFAKDGLOFJXMEN-UHFFFAOYSA-N 2-ethenyloxetane Chemical compound C=CC1CCO1 UFAKDGLOFJXMEN-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 229930014626 natural product Natural products 0.000 description 2
- 239000000575 pesticide Substances 0.000 description 2
- UVNPEUJXKZFWSJ-LMTQTHQJSA-N (R)-N-[(4S)-8-[6-amino-5-[(3,3-difluoro-2-oxo-1H-pyrrolo[2,3-b]pyridin-4-yl)sulfanyl]pyrazin-2-yl]-2-oxa-8-azaspiro[4.5]decan-4-yl]-2-methylpropane-2-sulfinamide Chemical compound CC(C)(C)[S@@](=O)N[C@@H]1COCC11CCN(CC1)c1cnc(Sc2ccnc3NC(=O)C(F)(F)c23)c(N)n1 UVNPEUJXKZFWSJ-LMTQTHQJSA-N 0.000 description 1
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- URUMMNOZQNJPBK-UHFFFAOYSA-N 2-ethenyl-1H-azepine Chemical compound C=CC1=CC=CC=CN1 URUMMNOZQNJPBK-UHFFFAOYSA-N 0.000 description 1
- VUAUSTRXYOQTOG-UHFFFAOYSA-N 4-ethenyl-4H-1,2-benzoxazin-3-one Chemical class C(=C)C1C(NOC2=C1C=CC=C2)=O VUAUSTRXYOQTOG-UHFFFAOYSA-N 0.000 description 1
- SBDYBCWCFWTRMA-UHFFFAOYSA-N 4-ethenyl-5h-1,3-oxazol-2-one Chemical class C=CC1=NC(=O)OC1 SBDYBCWCFWTRMA-UHFFFAOYSA-N 0.000 description 1
- NUSWDRHNSBBEEO-UHFFFAOYSA-N 4-methylidene-1,3-oxazolidin-2-one Chemical class C=C1COC(=O)N1 NUSWDRHNSBBEEO-UHFFFAOYSA-N 0.000 description 1
- HQQTZCPKNZVLFF-UHFFFAOYSA-N 4h-1,2-benzoxazin-3-one Chemical class C1=CC=C2ONC(=O)CC2=C1 HQQTZCPKNZVLFF-UHFFFAOYSA-N 0.000 description 1
- UPULOMQHYQDNNT-UHFFFAOYSA-N 5h-1,3-oxazol-2-one Chemical class O=C1OCC=N1 UPULOMQHYQDNNT-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- DCERHCFNWRGHLK-UHFFFAOYSA-N C[Si](C)C Chemical group C[Si](C)C DCERHCFNWRGHLK-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- GXBYFVGCMPJVJX-UHFFFAOYSA-N Epoxybutene Chemical compound C=CC1CO1 GXBYFVGCMPJVJX-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 150000001260 acyclic compounds Chemical class 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
- 229910000024 caesium carbonate Inorganic materials 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 230000006324 decarbonylation Effects 0.000 description 1
- 238000006606 decarbonylation reaction Methods 0.000 description 1
- 238000006114 decarboxylation reaction Methods 0.000 description 1
- BEPAFCGSDWSTEL-UHFFFAOYSA-N dimethyl malonate Chemical compound COC(=O)CC(=O)OC BEPAFCGSDWSTEL-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- YIWFBNMYFYINAD-UHFFFAOYSA-N ethenylcyclopropane Chemical compound C=CC1CC1 YIWFBNMYFYINAD-UHFFFAOYSA-N 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 150000003951 lactams Chemical class 0.000 description 1
- 150000002596 lactones Chemical class 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- RMGJCSHZTFKPNO-UHFFFAOYSA-M magnesium;ethene;bromide Chemical compound [Mg+2].[Br-].[CH-]=C RMGJCSHZTFKPNO-UHFFFAOYSA-M 0.000 description 1
- 230000005415 magnetization Effects 0.000 description 1
- 239000008204 material by function Substances 0.000 description 1
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
- 239000012434 nucleophilic reagent Substances 0.000 description 1
- LIGACIXOYTUXAW-UHFFFAOYSA-N phenacyl bromide Chemical compound BrCC(=O)C1=CC=CC=C1 LIGACIXOYTUXAW-UHFFFAOYSA-N 0.000 description 1
- 229940093956 potassium carbonate Drugs 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000007142 ring opening reaction Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 238000005809 transesterification reaction Methods 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/26—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D307/30—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member 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
- C07D307/32—Oxygen atoms
- C07D307/33—Oxygen atoms in position 2, the oxygen atom being in its keto or unsubstituted enol form
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/16—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D309/28—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member 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
- C07D309/30—Oxygen atoms, e.g. delta-lactones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/76—Benzo[c]pyrans
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D313/00—Heterocyclic compounds containing rings of more than six members having one oxygen atom as the only ring hetero atom
- C07D313/02—Seven-membered rings
- C07D313/06—Seven-membered rings condensed with carbocyclic rings or ring systems
- C07D313/08—Seven-membered rings condensed with carbocyclic rings or ring systems condensed with one six-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
- C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
- C07D491/052—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being six-membered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
- C07D493/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
烯基内酯类化合物及其合成制备。该新型烯基内酯类化合物可用于金属钯催化剂催化的环化反应合成碳环、杂环化合物，也可用于金属钯催化剂催化的烯丙基化反应合成烯丙基取代的化合物。这种烯基内酯类化合物的结构式如(I)或(II)所示：
Description
技术领域
本发明涉及新型烯基内酯化合物及其合成制备。
背景技术
金属钯催化剂催化的环化反应可高效合成碳环、杂环化合物，金属钯催化剂催化的烯丙基化反应也可高效合成烯丙基化合物，这些反应具有高效、催化剂用量低、立体选择性好等优势，已在合成医药、农药、功能材料、天然产物及生物活性化合物中得到广泛应用。
在钯催化的反应中，基于烯丙基钯两性离子中间体的环化反应是一类重要的反应，已成为合成碳环、杂环化合物以及天然产物的重要工具之一。一般而言，以烯丙基钯两性离子作为活性中间体的催化环化反应起始于钯催化剂与烯丙基钯两性离子前体的作用，由此产生的两性离子活性中间体与贫电试剂进一步反应生成目标产物并再生钯催化剂完成催化循环。
依据结构，π-烯丙基钯两性离子前体化合物大致可以概括为三种类型，一类是非环状的羧酸酯、碳酸酯、三亚甲基甲烷等，通过脱羧、脱三甲基硅基类官能团生成烯丙基钯两性离子；第二类是烯基高张力环状分子，例如乙烯基环丙烷、乙烯基环氧乙烷、乙烯基环氧丁烷、乙烯基氮杂环丙烷、乙烯基氧杂环丁烷等，在钯催化下通过高张力环开环形成π-烯丙基钯两性离子；第三类是烯基或者亚甲基环状碳酸酯、噁唑啉酮、苯并噁嗪酮等，如亚甲基环状碳酸酯、亚甲基噁唑烷酮、亚甲基内酯、乙烯基环状碳酸酯、乙烯基噁唑啉酮、γ-亚甲基取代内酯、γ-亚甲基取代内酰胺、乙烯基苯并噁嗪酮等，在钯催化下通过脱羰反应形成π-烯丙基钯两性离子。这些烯丙基钯两性离子不仅可以作为三元合成子参与[3+n]环化反应，还可以作为一元、四元、五元、六元等合成子完成[2+1]、[4+1]、[4+2]、[4+3]、[5+1]、[5+2]、[5+3]、[5+4]、[6+3]、[6+4]及[8+2]等多样性的环化反应，为合成各类环状化合物提供了经济高效的途径。此外，这些前体化合物中的很多种类也可以用于烯丙基化反应来合成烯丙基化合物。
尽管已有多种可用于钯催化反应的可生成π-烯丙基钯两性离子的前体化合物，但是构建新颖的前体化合物将能够解决目前尚未实现合成的碳环或者杂环化合物以及烯丙基化合物的合成；尤其是以烯基内酯类化合物作为六元甚至更多元合成子来合成中环或者大环化合物尚属于空白领域。
发明内容
本发明的目的在于提供新型烯基内酯类化合物及其合成制备方法。
根据本发明的烯基内酯类化合物的结构通式如化学式(I)或化学式(II)所示：
其中，R1、R2、R3、R4、R5分别选自C1-60的烷基、C3-60的环烷基、C1-60的烷氧基、C2-60的烯基、C3-60的环烯基、取代或非取代的C3-60的炔基、H、F、Cl、Br、CF3、C2F5、NO2、CN、SO3H、苯基或取代苯基、苄基或者取代苄基、五元杂环基、六元杂环基、吲哚基、靛红基、苯并呋喃基、CF3以及C2F5中的任一种，EWG选自酯基CO2R6、酮羰基COR7、CHO、CN、NO2、SO2Ph、CF3和C2F5中的任一种，n＝0、1、2、3、4或5，m＝0、1、2或3，R6选自C1-60的烷基、C3-60的环烷基、C2-60的烯基、C3-60的环烯基、取代或非取代的C3-60的炔基、苯基或取代苯基、苄基或者取代苄基、五元杂环基、六元杂环基、吲哚基、靛红基、苯并呋喃基、CF3和C2F5中的任一种，R7选自C1-60的烷基、C3-60的环烷基、C2-60的烯基、C3-60的环烯基、取代或非取代的C3-60的炔基、苯基或取代苯基、苄基或取代苄基、五元杂环基、六元杂环基、吲哚基、靛红基、苯并呋喃基、CF3和C2F5中的任一种，结构式(II)中并环为环烷基、苯基或杂芳基。
根据本发明的烯基内酯类化合物，并环优选均为C3-30脂肪族环或3-10元的芳香族环，所述脂肪族环或芳香族环中的至少一个碳原子替换为氮、氧、硅及硫中的任一种。
根据本发明的化学式(I)的化合物的合成方法如下：
具体步骤如下：
(1)将化合物1、化合物2以及碳酸钾加至丙酮中，室温搅拌，TLC(薄层色谱)检测反应完全后，浓缩溶液，加水，二氯甲烷萃取若干次，有机相用饱和氯化钠溶液洗涤若干次例如3次，无水硫酸钠干燥，用无水甲醇重结晶，真空干燥得化合物3(产率80-90％)；
(2)将化合物3加至四氢呋喃中，并在冰浴冷却下搅拌10min，缓慢滴加格氏试剂烯基溴化镁，升至室温反应，TLC检测反应完全后，冰浴下滴加饱和氯化铵溶液淬灭，并用乙酸乙酯萃取，有机相依次用饱和碳酸氢钠溶液、饱和氯化钠溶液洗涤，无水硫酸钠干燥，用旋转蒸发仪真空浓缩，柱层析得化合物4(产率80-96％)；
(3)将化合物4以及4-二甲氨基吡啶(DMAP)加至无水乙醇中，室温搅拌，TLC检测反应完全后，浓缩溶液，二氯甲烷萃取若干次例如3次，有机相用饱和氯化钠溶液洗涤若干次例如3次，无水硫酸钠干燥，用旋转蒸发仪真空浓缩，柱层析得化学式(I)的化合物(产率75-90％)。
根据本发明的合成方法，步骤(1)中，化合物1、化合物2、碳酸钾的摩尔比为1:2:1，反应时间为1-120小时，优选为2-48小时，反应温度为-40℃至40℃。
根据本发明的合成方法，步骤(2)中，化合物3与格氏试剂的摩尔比为1:(1-10)，优选为1:(1-2.5)，反应时间为0.1-120小时，优选为2-24小时，反应温度为-40℃至60℃。
根据本发明的合成方法，步骤(3)中，化合物4与DMAP的摩尔比为100:(1-200)，优选为100:(10-30)，反应时间为1-120小时，优选为2-24小时，反应温度为-40℃至60℃。
步骤(3)中，碱包括但不限于4-二甲氨基吡啶、吡啶、三乙胺、碳酸铯、氢氧化钾、叔丁醇钾、甲醇钠。
步骤(3)中，酯交换措施优选包括使用离子交换树脂。
本发明中的烯基内酯类化合物可以在金属钯的作用下发生脱羧或未脱羧的π-烯丙基钯两性离子，可以与亲电试剂构建环状化合物，也可以与亲核试剂构建烯丙基取代的化合物。
根据本发明的化合物，碳原子总数为1-60烷基、烷氧基的碳原子总数优选为2-8，所述碳原子总数为2-60烯基的碳原子总数优选为2-8，碳原子总数为3-60环烷基、环烯基、炔基的碳原子总数优选为3-10，所述并环结构优选苯环、或环己基。
所述的取代苯基、取代苄基中的取代基至少为氟、氯、溴、碘、硝基、氰基、烷基、烷氧基，三氟甲基中的至少一种。
本发明中化学式(I)或(II)所示的烯基内酯类化合物可优选自以下具体结构中的一种：
本发明具有以下优点：
1本发明所得的新型烯基内酯化合物可作为钯催化反应的前体化合物，是具有新颖结构的前体化合物，用其可进行环化反应高效合成碳环、杂环化合物以及烯丙基取代的化合物；
2本发明所得的新型烯基内酯化合物在金属钯催化下可以在手性配体的控制下获得光学纯的碳环、杂环以及非环状化合物；
3本发明所得的新型烯基内酯化合物参与的反应操作简便，副反应少，便于分离提纯，且可放大量制备；
4本发明为合成新的具有潜在生物活性的碳环、杂环或非环状化合物提供了一种新的途径，并且有希望制备高活性的医药或农药活性化合物。
具体实施方式
下面以制备化学式(I)的化合物10为例，对本发明作出进一步描述。
化合物10的合成示意如下：
(1)取250mL的单口烧瓶，加入化合物5α-溴代苯乙酮(6g，30mmol)，化合物6丙二酸二甲酯(7.92g，60mmol)，碳酸钾(4.14g，30mmol)，并加入60mL丙酮，室温搅拌12小时，TLC检测反应完全后，浓缩溶液，加水，二氯甲烷萃取三次，饱和氯化钠溶液洗涤三次，有机相用无水硫酸钠干燥，用无水甲醇重结晶，真空干燥得化合物7(白色固体，6.3g，产率84％)。
(2)取125mL的三口烧瓶，加入化合物7(2.5g，10mmol)，置换氩气保护，加入10mL四氢呋喃并在冰浴冷却下搅拌10分钟，缓慢滴加化合物8乙烯基溴化镁(20mL，1M的THF溶液，10mmol)，升至室温反应2小时，TLC检测反应完全后，冰浴下滴加饱和氯化铵溶液淬灭，并用乙酸乙酯萃取，依次用饱和碳酸氢钠溶液、饱和氯化钠溶液洗涤，有机相用无水硫酸钠干燥，真空浓缩，柱层析得化合物9(黄色油状液体，2.7g，产率96％)。
(3)取125mL的单口烧瓶，加入化合物9(2.78g，10mmol)，4-二甲氨基吡啶(2.44g，20mmol)，并加入30mL无水乙醇，室温搅拌12小时，TLC检测反应完全后，浓缩溶液，二氯甲烷萃取三次，饱和氯化钠溶液洗涤三次，有机相用无水硫酸钠干燥，真空浓缩，柱层析得化合物10(无色透明液体，2.1g，产率84％)。
化合物10的核磁如下：
1H NMR(300MHz,CDCl3)δ7.85–7.72(m,2H),7.43(dd,J＝9.1,3.4Hz,1H),7.37–7.26(m,7H),7.17(td,J＝7.6,1.5Hz,1H),7.06(td,J＝7.5,1.4Hz,1H),7.00(dd,J＝7.8,1.3Hz,1H),6.89(s,1H),6.80(dd,J＝7.6,1.5Hz,1H),6.05(d,J＝0.8Hz,1H),4.92(d,J＝10.3Hz,1H),4.19(q,J＝7.1Hz,2H),3.03(ddd,J＝14.5,11.2,2.8Hz,1H),2.56–2.33(m,4H),1.25(t,J＝7.1Hz,3H).
13CNMR(75MHz,CDCl3)δ165.3,149.1,144.7,141.7,139.0,135.8,134.5,134.4,129.9,128.9,128.7,128.6,128.1,127.7,125.7,125.4,125.2,124.7,61.6,61.4,57.3,38.5,21.5,13.9.
由上所列核磁数据可知，所得产物结构正确。
Claims (7)
1.一种烯基内酯类化合物，其结构通式如化学式(I)或化学式(II)所示：
其中，R1、R2、R3、R4、R5分别选自C1-60的烷基、C3-60的环烷基、C1-60的烷氧基、C2-60的烯基、C3-60的环烯基、取代或非取代的C3-60的炔基、H、F、Cl、Br、CF3、C2F5、NO2、CN、SO3H、苯基或取代苯基、苄基或者取代苄基、五元杂环基、六元杂环基、吲哚基、靛红基、苯并呋喃基、CF3以及C2F5中的任一种，EWG选自酯基CO2R6、酮羰基COR7、CHO、CN、NO2、SO2Ph、CF3和C2F5中的任一种，n＝0、1、2、3、4或5，m＝0、1、2或3，R6选自C1-60的烷基、C3-60的环烷基、C2-60的烯基、C3-60的环烯基、取代或非取代的C3-60的炔基、苯基或取代苯基、苄基或者取代苄基、五元杂环基、六元杂环基、吲哚基、靛红基、苯并呋喃基、CF3和C2F5中的任一种，R7选自C1-60的烷基、C3-60的环烷基、C2-60的烯基、C3-60的环烯基、取代或非取代的C3-60的炔基、苯基或取代苯基、苄基或取代苄基、五元杂环基、六元杂环基、吲哚基、靛红基、苯并呋喃基、CF3和C2F5中的任一种，结构式(II)中并环为环烷基、苯基或杂芳基。
2.根据权利要求1所述的烯基内酯类化合物，并环均为C3-30脂肪族环或3-10元的芳香族环，所述脂肪族环或芳香族环中的至少一个碳原子替换为氮、氧、硅及硫中的任一种。
3.如权利要求1所述的化合物的合成方法，包括以下步骤：
所述化学式(I)的化合物的合成方法如下：
具体步骤如下：
(1)将化合物1、化合物2以及碳酸钾加至丙酮中，室温搅拌，TLC(薄层色谱)检测反应完全后，浓缩溶液，加水，二氯甲烷萃取若干次，有机相用饱和氯化钠溶液洗涤若干次，无水硫酸钠干燥，用无水甲醇重结晶，真空干燥得化合物3；
(2)将化合物3加至四氢呋喃中，并在冰浴冷却下搅拌10min，缓慢滴加格氏试剂烯基溴化镁，升至室温反应，TLC检测反应完全后，冰浴下滴加饱和氯化铵溶液淬灭，并用乙酸乙酯萃取，有机相依次用饱和碳酸氢钠溶液、饱和氯化钠溶液洗涤，无水硫酸钠干燥，用旋转蒸发仪真空浓缩，柱层析得化合物4；
(3)将化合物4以及4-二甲氨基吡啶(DMAP)加至无水乙醇中，室温搅拌，TLC检测反应完全后，浓缩溶液，二氯甲烷萃取若干次，有机相用饱和氯化钠溶液洗涤若干次，无水硫酸钠干燥，用旋转蒸发仪真空浓缩，柱层析得化学式(I)的化合物。
4.根据权利要求3所述的化合物的合成方法，其特征在于，步骤(1)中，化合物1、化合物2、碳酸钾的摩尔比为1:2:1，反应时间为1-120小时，反应温度为-40℃至40℃。
5.根据权利要求3所述的内酯类化合物的合成方法，其特征在于，步骤(2)中，化合物3与格氏试剂的摩尔比为1:(1-10)，反应时间为0.1-120小时，反应温度为-40℃至60℃。
6.根据权利要求3所述的化合物的合成方法，其特征在于，步骤(3)中，化合物4与DMAP的摩尔比为100:(1-200)，反应时间为1-120小时，反应温度为-40℃至60℃。
7.根据权利要求3-5之一所述合成方法制备的烯基内酯类化合物。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110464424.3A CN115246800A (zh) | 2021-04-28 | 2021-04-28 | 烯基内酯类化合物及其合成制备 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110464424.3A CN115246800A (zh) | 2021-04-28 | 2021-04-28 | 烯基内酯类化合物及其合成制备 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN115246800A true CN115246800A (zh) | 2022-10-28 |
Family
ID=83697570
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110464424.3A Pending CN115246800A (zh) | 2021-04-28 | 2021-04-28 | 烯基内酯类化合物及其合成制备 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115246800A (zh) |
-
2021
- 2021-04-28 CN CN202110464424.3A patent/CN115246800A/zh active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Zheng et al. | Highly Efficient Asymmetric Epoxidation of Electron‐Deficient α, β‐Enones and Related Applications to Organic Synthesis | |
| CN111205279B (zh) | 一种多取代苯并二氢呋喃并杂环类化合物及其制备方法和应用 | |
| CN108690030A (zh) | 具有光学活性的吡咯硫酮结构的螺环氧化吲哚类化合物及其合成方法 | |
| CN108314658B (zh) | 一种多取代噁唑衍生物的制备方法 | |
| Zhu et al. | Organocatalytic Asymmetric Formal [3+ 3] Cycloaddition Reactions of α, β‐Unsaturated Aldehydes with Nazarov Reagents | |
| Ichikawa et al. | Stereocontrolled synthesis of cytotoxic anhydrosphingosine pachastrissamine by using [3.3] sigmatropic rearrangement of allyl cyanate | |
| Ni et al. | Highly enantioselective Michael addition of ketones to nitroolefins catalyzed by (S)-pyrrolidine arenesulfonamide | |
| CN109096162B (zh) | 一种钪催化硫醇对邻亚甲基苯醌的亲核加成反应方法 | |
| CN115246800A (zh) | 烯基内酯类化合物及其合成制备 | |
| CN108912076B (zh) | 一种苯并氧杂环化合物的合成方法 | |
| CN111646964A (zh) | 一种碱催化的合成2h-吡喃-2-酮衍生物新方法 | |
| CN108864115B (zh) | [3+2]环加成不对称脱芳构化合成手性非芳香嘌呤核苷的方法 | |
| CN113004233B (zh) | 一种用于制备prc2抑制剂的化合物、其制备方法和用途 | |
| CN110240572B (zh) | 一种反式-1,1-环丙烷二羧酸酯的合成方法 | |
| CN101343263A (zh) | 一种合成5-硝基-4,5-二氢呋喃衍生物的方法 | |
| CN111732552A (zh) | 一种钯催化合成1,3-噁唑-2-硫酮的方法 | |
| CN104892557A (zh) | 一种不对称合成手性二氢香豆素衍生物的方法 | |
| Otero et al. | Preliminary studies on the synthesis of rancinamycins from nitrosugars: first total synthesis of (3S, 4S, 5S, 6R)-5-benzyloxy-6-hydroxy-3, 4-(isopropylidendioxy)-cyclohex-1-enecarbaldehyde | |
| CN110467622A (zh) | 一种新型曲酸并呋喃类化合物及其制备方法 | |
| CN112939830B (zh) | 一种烯基硫醚对邻亚甲基苯醌的亲核反应方法 | |
| CN110467558B (zh) | 一种镍催化合成3-胺基异吲哚啉酮的反应方法 | |
| Pitsch et al. | Synthesis of a functionalized cyclohepten-one from erythronic acid-4-lactone | |
| CN110467556B (zh) | 一种镍催化亚胺离子与苯乙酮的亲核反应方法 | |
| CN110804007B (zh) | 一种多取代吡咯衍生物及其制备方法 | |
| CN112745275B (zh) | 1,3,4-恶二唑杂环化合物的合成方法 |
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 |