CN115385948A - Spiro-dihydrobenzothiole bisoxazoline compound, preparation method and application thereof - Google Patents
Spiro-dihydrobenzothiole bisoxazoline compound, preparation method and application thereof Download PDFInfo
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- CN115385948A CN115385948A CN202211048523.4A CN202211048523A CN115385948A CN 115385948 A CN115385948 A CN 115385948A CN 202211048523 A CN202211048523 A CN 202211048523A CN 115385948 A CN115385948 A CN 115385948A
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- alkyl
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 235
- 238000002360 preparation method Methods 0.000 title claims abstract description 16
- 238000006713 insertion reaction Methods 0.000 claims abstract description 65
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 51
- 239000001257 hydrogen Substances 0.000 claims abstract description 50
- 238000006243 chemical reaction Methods 0.000 claims abstract description 44
- 125000000217 alkyl group Chemical group 0.000 claims description 194
- -1 Alkyl radical Chemical class 0.000 claims description 138
- 239000000460 chlorine Substances 0.000 claims description 118
- 125000003118 aryl group Chemical group 0.000 claims description 93
- 229910052736 halogen Inorganic materials 0.000 claims description 84
- 150000002367 halogens Chemical class 0.000 claims description 84
- 125000005842 heteroatom Chemical group 0.000 claims description 84
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 68
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 62
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 44
- 125000003545 alkoxy group Chemical group 0.000 claims description 44
- 229910052760 oxygen Inorganic materials 0.000 claims description 41
- 229910052717 sulfur Inorganic materials 0.000 claims description 41
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 37
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 36
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 35
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 33
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 32
- 239000003513 alkali Substances 0.000 claims description 32
- 125000004432 carbon atom Chemical group C* 0.000 claims description 31
- 239000003960 organic solvent Substances 0.000 claims description 31
- 239000002904 solvent Substances 0.000 claims description 31
- 229910052763 palladium Inorganic materials 0.000 claims description 30
- 239000003054 catalyst Substances 0.000 claims description 28
- 150000002431 hydrogen Chemical class 0.000 claims description 28
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 27
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 27
- 239000003446 ligand Substances 0.000 claims description 25
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 24
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 22
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 22
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 19
- 238000007112 amidation reaction Methods 0.000 claims description 19
- 239000011737 fluorine Substances 0.000 claims description 19
- 229910052731 fluorine Inorganic materials 0.000 claims description 19
- 239000002808 molecular sieve Substances 0.000 claims description 19
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 18
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 claims description 18
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 18
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 18
- 238000000034 method Methods 0.000 claims description 18
- 125000001424 substituent group Chemical group 0.000 claims description 18
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 17
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 17
- 125000001931 aliphatic group Chemical group 0.000 claims description 17
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 17
- 229910052794 bromium Inorganic materials 0.000 claims description 17
- 229910052801 chlorine Inorganic materials 0.000 claims description 17
- 150000008282 halocarbons Chemical class 0.000 claims description 17
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 17
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 17
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 17
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims description 16
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 16
- 125000000623 heterocyclic group Chemical group 0.000 claims description 16
- 150000003839 salts Chemical class 0.000 claims description 16
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 15
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 15
- 238000003402 intramolecular cyclocondensation reaction Methods 0.000 claims description 14
- 229910052751 metal Inorganic materials 0.000 claims description 14
- 239000000203 mixture Substances 0.000 claims description 14
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
- 239000003153 chemical reaction reagent Substances 0.000 claims description 13
- 239000010949 copper Substances 0.000 claims description 13
- 239000002184 metal Substances 0.000 claims description 13
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 claims description 13
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 claims description 13
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 13
- GETTZEONDQJALK-UHFFFAOYSA-N (trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC=C1 GETTZEONDQJALK-UHFFFAOYSA-N 0.000 claims description 12
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 claims description 12
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 claims description 12
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 claims description 12
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims description 12
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 12
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 claims description 12
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 12
- 239000003849 aromatic solvent Substances 0.000 claims description 12
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims description 12
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 claims description 12
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 claims description 12
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 claims description 12
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 claims description 12
- 125000002723 alicyclic group Chemical group 0.000 claims description 11
- 229910052802 copper Inorganic materials 0.000 claims description 11
- 125000001072 heteroaryl group Chemical group 0.000 claims description 11
- HZVOZRGWRWCICA-UHFFFAOYSA-N methanediyl Chemical compound [CH2] HZVOZRGWRWCICA-UHFFFAOYSA-N 0.000 claims description 11
- 125000001624 naphthyl group Chemical group 0.000 claims description 11
- 229910052757 nitrogen Inorganic materials 0.000 claims description 10
- 150000007530 organic bases Chemical class 0.000 claims description 10
- 238000003786 synthesis reaction Methods 0.000 claims description 10
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 9
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 9
- RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 claims description 9
- 238000005886 esterification reaction Methods 0.000 claims description 9
- KAVKNHPXAMTURG-UHFFFAOYSA-N n-(4-bromonaphthalen-1-yl)acetamide Chemical compound C1=CC=C2C(NC(=O)C)=CC=C(Br)C2=C1 KAVKNHPXAMTURG-UHFFFAOYSA-N 0.000 claims description 9
- 125000002541 furyl group Chemical group 0.000 claims description 8
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 8
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims description 8
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 8
- 125000004076 pyridyl group Chemical group 0.000 claims description 8
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 8
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical class ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 claims description 8
- 125000001544 thienyl group Chemical group 0.000 claims description 8
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 7
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 7
- 125000005843 halogen group Chemical group 0.000 claims description 7
- 150000007529 inorganic bases Chemical class 0.000 claims description 7
- 229910052740 iodine Inorganic materials 0.000 claims description 7
- 239000011630 iodine Substances 0.000 claims description 7
- LVEYOSJUKRVCCF-UHFFFAOYSA-N 1,3-bis(diphenylphosphino)propane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCP(C=1C=CC=CC=1)C1=CC=CC=C1 LVEYOSJUKRVCCF-UHFFFAOYSA-N 0.000 claims description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 6
- SGUVLZREKBPKCE-UHFFFAOYSA-N 1,5-diazabicyclo[4.3.0]-non-5-ene Chemical compound C1CCN=C2CCCN21 SGUVLZREKBPKCE-UHFFFAOYSA-N 0.000 claims description 6
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 claims description 6
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims description 6
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 claims description 6
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-diisopropylethylamine Substances CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 6
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 6
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 6
- WXNOJTUTEXAZLD-UHFFFAOYSA-L benzonitrile;dichloropalladium Chemical compound Cl[Pd]Cl.N#CC1=CC=CC=C1.N#CC1=CC=CC=C1 WXNOJTUTEXAZLD-UHFFFAOYSA-L 0.000 claims description 6
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 6
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 6
- 239000004210 ether based solvent Substances 0.000 claims description 6
- DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 claims description 6
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 claims description 6
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 claims description 6
- WGOPGODQLGJZGL-UHFFFAOYSA-N lithium;butane Chemical compound [Li+].CC[CH-]C WGOPGODQLGJZGL-UHFFFAOYSA-N 0.000 claims description 6
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 claims description 6
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 claims description 6
- 239000003208 petroleum Substances 0.000 claims description 6
- 235000011056 potassium acetate Nutrition 0.000 claims description 6
- IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 claims description 6
- 229910000160 potassium phosphate Inorganic materials 0.000 claims description 6
- 235000011009 potassium phosphates Nutrition 0.000 claims description 6
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 6
- 229910052710 silicon Inorganic materials 0.000 claims description 6
- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 claims description 6
- 239000012312 sodium hydride Substances 0.000 claims description 6
- 229910000104 sodium hydride Inorganic materials 0.000 claims description 6
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 claims description 6
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 claims description 6
- SIOVKLKJSOKLIF-HJWRWDBZSA-N trimethylsilyl (1z)-n-trimethylsilylethanimidate Chemical compound C[Si](C)(C)OC(/C)=N\[Si](C)(C)C SIOVKLKJSOKLIF-HJWRWDBZSA-N 0.000 claims description 6
- 239000008096 xylene Substances 0.000 claims description 6
- JEYCPFDCZQPYBL-UHFFFAOYSA-N 2-diazo-2-phenylacetic acid Chemical compound OC(=O)C(=[N+]=[N-])C1=CC=CC=C1 JEYCPFDCZQPYBL-UHFFFAOYSA-N 0.000 claims description 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
- 239000011261 inert gas Substances 0.000 claims description 5
- UKSZBOKPHAQOMP-SVLSSHOZSA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 UKSZBOKPHAQOMP-SVLSSHOZSA-N 0.000 claims description 4
- CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 claims description 4
- PAGZTSLSNQZYEV-UHFFFAOYSA-L 2,2-dimethylpropanoate;palladium(2+) Chemical compound [Pd+2].CC(C)(C)C([O-])=O.CC(C)(C)C([O-])=O PAGZTSLSNQZYEV-UHFFFAOYSA-L 0.000 claims description 4
- FAFGMAGIYHHRKN-UHFFFAOYSA-N 2-diphenylphosphanylethyl(diphenyl)phosphane;palladium Chemical compound [Pd].C=1C=CC=CC=1P(C=1C=CC=CC=1)CCP(C=1C=CC=CC=1)C1=CC=CC=C1.C=1C=CC=CC=1P(C=1C=CC=CC=1)CCP(C=1C=CC=CC=1)C1=CC=CC=C1 FAFGMAGIYHHRKN-UHFFFAOYSA-N 0.000 claims description 4
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 4
- 239000012359 Methanesulfonyl chloride Substances 0.000 claims description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 4
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 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 4
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 claims description 4
- QTMDXZNDVAMKGV-UHFFFAOYSA-L copper(ii) bromide Chemical compound [Cu+2].[Br-].[Br-] QTMDXZNDVAMKGV-UHFFFAOYSA-L 0.000 claims description 4
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 4
- YNHIGQDRGKUECZ-UHFFFAOYSA-N dichloropalladium;triphenylphosphanium Chemical compound Cl[Pd]Cl.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-N 0.000 claims description 4
- 150000002739 metals Chemical class 0.000 claims description 4
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- JGBZTJWQMWZVNX-UHFFFAOYSA-N palladium;tricyclohexylphosphane Chemical compound [Pd].C1CCCCC1P(C1CCCCC1)C1CCCCC1.C1CCCCC1P(C1CCCCC1)C1CCCCC1 JGBZTJWQMWZVNX-UHFFFAOYSA-N 0.000 claims description 4
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 claims description 4
- 125000004193 piperazinyl group Chemical group 0.000 claims description 4
- 125000003386 piperidinyl group Chemical group 0.000 claims description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
- 239000010703 silicon Substances 0.000 claims description 4
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 claims description 4
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical group FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 claims description 4
- 229910021589 Copper(I) bromide Inorganic materials 0.000 claims description 3
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 claims description 3
- 229910052786 argon Inorganic materials 0.000 claims description 3
- 125000002837 carbocyclic group Chemical group 0.000 claims description 3
- 150000004696 coordination complex Chemical class 0.000 claims description 3
- NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 claims description 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
- 238000011065 in-situ storage Methods 0.000 claims description 3
- 229910052709 silver Inorganic materials 0.000 claims description 3
- 239000004332 silver Substances 0.000 claims description 3
- 229910001494 silver tetrafluoroborate Inorganic materials 0.000 claims description 3
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 3
- 125000003554 tetrahydropyrrolyl group Chemical group 0.000 claims description 3
- OZDCZHDOIBUGAJ-UHFFFAOYSA-N 4-(trifluoromethyl)benzenesulfonyl chloride Chemical compound FC(F)(F)C1=CC=C(S(Cl)(=O)=O)C=C1 OZDCZHDOIBUGAJ-UHFFFAOYSA-N 0.000 claims description 2
- 229910021591 Copper(I) chloride Inorganic materials 0.000 claims description 2
- 229910021595 Copper(I) iodide Inorganic materials 0.000 claims description 2
- 229910021590 Copper(II) bromide Inorganic materials 0.000 claims description 2
- PMPVIKIVABFJJI-UHFFFAOYSA-N Cyclobutane Chemical compound C1CCC1 PMPVIKIVABFJJI-UHFFFAOYSA-N 0.000 claims description 2
- LVZWSLJZHVFIQJ-UHFFFAOYSA-N Cyclopropane Chemical compound C1CC1 LVZWSLJZHVFIQJ-UHFFFAOYSA-N 0.000 claims description 2
- SOTVPQOAZNKYSI-UHFFFAOYSA-N benzene;trifluoromethanesulfonic acid Chemical compound C1=CC=CC=C1.OS(=O)(=O)C(F)(F)F SOTVPQOAZNKYSI-UHFFFAOYSA-N 0.000 claims description 2
- CSKNSYBAZOQPLR-UHFFFAOYSA-N benzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=C1 CSKNSYBAZOQPLR-UHFFFAOYSA-N 0.000 claims description 2
- 125000001246 bromo group Chemical group Br* 0.000 claims description 2
- 238000006555 catalytic reaction Methods 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 claims description 2
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 claims description 2
- 229910000366 copper(II) sulfate Inorganic materials 0.000 claims description 2
- DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 claims description 2
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 claims description 2
- YRNNKGFMTBWUGL-UHFFFAOYSA-L copper(ii) perchlorate Chemical compound [Cu+2].[O-]Cl(=O)(=O)=O.[O-]Cl(=O)(=O)=O YRNNKGFMTBWUGL-UHFFFAOYSA-L 0.000 claims description 2
- 229960003280 cupric chloride Drugs 0.000 claims description 2
- 229940045803 cuprous chloride Drugs 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims description 2
- 125000002346 iodo group Chemical group I* 0.000 claims description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- YPWUSCQEBOYEFU-UHFFFAOYSA-N toluene;trifluoromethanesulfonic acid Chemical compound CC1=CC=CC=C1.OS(=O)(=O)C(F)(F)F YPWUSCQEBOYEFU-UHFFFAOYSA-N 0.000 claims description 2
- FFBHFFJDDLITSX-UHFFFAOYSA-N benzyl N-[2-hydroxy-4-(3-oxomorpholin-4-yl)phenyl]carbamate Chemical compound OC1=C(NC(=O)OCC2=CC=CC=C2)C=CC(=C1)N1CCOCC1=O FFBHFFJDDLITSX-UHFFFAOYSA-N 0.000 claims 1
- SBTSVTLGWRLWOD-UHFFFAOYSA-L copper(ii) triflate Chemical compound [Cu+2].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F SBTSVTLGWRLWOD-UHFFFAOYSA-L 0.000 claims 1
- WZZMHOBVLAEJOD-UHFFFAOYSA-N methylsulfanylmethane;hydrobromide Chemical compound [Br-].C[SH+]C WZZMHOBVLAEJOD-UHFFFAOYSA-N 0.000 claims 1
- 230000006698 induction Effects 0.000 abstract description 5
- 125000000664 diazo group Chemical group [N-]=[N+]=[*] 0.000 abstract 1
- 239000007787 solid Substances 0.000 description 101
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 24
- 239000000047 product Substances 0.000 description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- 238000004128 high performance liquid chromatography Methods 0.000 description 9
- 238000004809 thin layer chromatography Methods 0.000 description 7
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 125000004429 atom Chemical group 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 229920006395 saturated elastomer Polymers 0.000 description 5
- 125000003003 spiro group Chemical group 0.000 description 5
- CSCPPACGZOOCGX-MICDWDOJSA-N 1-deuteriopropan-2-one Chemical compound [2H]CC(C)=O CSCPPACGZOOCGX-MICDWDOJSA-N 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 125000004122 cyclic group Chemical group 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 238000012216 screening Methods 0.000 description 4
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 4
- HYAAEBUKCXOFDT-UHFFFAOYSA-N 2-diazonio-1-methoxy-2-phenylethenolate Chemical compound COC(=O)C(=[N+]=[N-])C1=CC=CC=C1 HYAAEBUKCXOFDT-UHFFFAOYSA-N 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- QDZARNQKIZUXDK-UHFFFAOYSA-N [C-][N+]#N Chemical class [C-][N+]#N QDZARNQKIZUXDK-UHFFFAOYSA-N 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 238000004821 distillation Methods 0.000 description 3
- 150000002430 hydrocarbons Chemical group 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- 101150003085 Pdcl gene Proteins 0.000 description 2
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical group C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- QMMFVYPAHWMCMS-UHFFFAOYSA-N dimethyl monosulfide Natural products CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 125000002950 monocyclic group Chemical group 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 125000003367 polycyclic group Chemical group 0.000 description 2
- 238000010791 quenching Methods 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 125000006413 ring segment Chemical group 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- ZXMGHDIOOHOAAE-UHFFFAOYSA-N 1,1,1-trifluoro-n-(trifluoromethylsulfonyl)methanesulfonamide Chemical compound FC(F)(F)S(=O)(=O)NS(=O)(=O)C(F)(F)F ZXMGHDIOOHOAAE-UHFFFAOYSA-N 0.000 description 1
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
- 238000006845 Michael addition reaction Methods 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- HWUPLUNLNUHIQZ-UHFFFAOYSA-N copper;trifluoromethanesulfonic acid Chemical compound [Cu].OS(=O)(=O)C(F)(F)F.OS(=O)(=O)C(F)(F)F HWUPLUNLNUHIQZ-UHFFFAOYSA-N 0.000 description 1
- 238000005888 cyclopropanation reaction Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical compound [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- MXQOYLRVSVOCQT-UHFFFAOYSA-N palladium;tritert-butylphosphane Chemical compound [Pd].CC(C)(C)P(C(C)(C)C)C(C)(C)C.CC(C)(C)P(C(C)(C)C)C(C)(C)C MXQOYLRVSVOCQT-UHFFFAOYSA-N 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000009987 spinning Methods 0.000 description 1
- FHTXZDURQDIVCD-UHFFFAOYSA-N spiro[4.4]nona-1,3-diene Chemical compound C1CCCC21C=CC=C2 FHTXZDURQDIVCD-UHFFFAOYSA-N 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/0803—Compounds with Si-C or Si-Si linkages
- C07F7/081—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te
- C07F7/0812—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te comprising a heterocyclic ring
- C07F7/0816—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te comprising a heterocyclic ring said ring comprising Si as a ring atom
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/18—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms
- B01J31/1805—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms the ligands containing nitrogen
- B01J31/181—Cyclic ligands, including e.g. non-condensed polycyclic ligands, comprising at least one complexing nitrogen atom as ring member, e.g. pyridine
- B01J31/184—Cyclic ligands, including e.g. non-condensed polycyclic ligands, comprising at least one complexing nitrogen atom as ring member, e.g. pyridine mixed aromatic/aliphatic ring systems, e.g. indoline
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B53/00—Asymmetric syntheses
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/04—Formation of amino groups in compounds containing carboxyl groups
- C07C227/06—Formation of amino groups in compounds containing carboxyl groups by addition or substitution reactions, without increasing the number of carbon atoms in the carbon skeleton of the acid
- C07C227/08—Formation of amino groups in compounds containing carboxyl groups by addition or substitution reactions, without increasing the number of carbon atoms in the carbon skeleton of the acid by reaction of ammonia or amines with acids containing functional groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/31—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by introduction of functional groups containing oxygen only in singly bound form
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/0803—Compounds with Si-C or Si-Si linkages
- C07F7/0825—Preparations of compounds not comprising Si-Si or Si-cyano linkages
- C07F7/083—Syntheses without formation of a Si-C bond
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
- B01J2231/40—Substitution reactions at carbon centres, e.g. C-C or C-X, i.e. carbon-hetero atom, cross-coupling, C-H activation or ring-opening reactions
- B01J2231/42—Catalytic cross-coupling, i.e. connection of previously not connected C-atoms or C- and X-atoms without rearrangement
- B01J2231/4277—C-X Cross-coupling, e.g. nucleophilic aromatic amination, alkoxylation or analogues
- B01J2231/4283—C-X Cross-coupling, e.g. nucleophilic aromatic amination, alkoxylation or analogues using N nucleophiles, e.g. Buchwald-Hartwig amination
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- B—PERFORMING OPERATIONS; TRANSPORTING
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- B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
- B01J2231/40—Substitution reactions at carbon centres, e.g. C-C or C-X, i.e. carbon-hetero atom, cross-coupling, C-H activation or ring-opening reactions
- B01J2231/42—Catalytic cross-coupling, i.e. connection of previously not connected C-atoms or C- and X-atoms without rearrangement
- B01J2231/4277—C-X Cross-coupling, e.g. nucleophilic aromatic amination, alkoxylation or analogues
- B01J2231/4288—C-X Cross-coupling, e.g. nucleophilic aromatic amination, alkoxylation or analogues using O nucleophiles, e.g. alcohols, carboxylates, esters
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- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
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- B01J2531/16—Copper
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Abstract
The invention discloses a spirobisdihydrobenzothiole bisoxazoline compound, a preparation method and application thereof. Specifically, the invention discloses a compound shown as a formula I or II. The preparation method of the compound shown as the formula I or II is simple and convenient to operate, and the compound can be used for asymmetric reactions such as asymmetric diazo carbene-heteroatom-hydrogen bondThe asymmetric insertion reaction shows excellent asymmetric induction capability or the yield of the asymmetric reaction in which the asymmetric insertion reaction participates is high.
Description
Technical Field
The invention relates to a spirobisdihydrobenzothiollo bisoxazoline compound, a preparation method and application thereof.
Background
Bisoxazoline is one of the most important ligands in metal-catalyzed asymmetric reactions, and has the main characteristics of easy synthesis and excellent asymmetric induction capability in various asymmetric reactions, such as copper-catalyzed Michael addition, diazo-olefin cyclopropanation and the like. Among the bisoxazolines, the spiro skeleton is one of the important bisoxazoline ligands, mainly because the unique rigid structure of the spiro skeleton makes the bisoxazoline ligand derived from the spiro skeleton have unique chemical reactivity. Ligands of spiro skeleton bisoxazoline ligands (spiro rings such as spiroindane and spiro [4.4] nonadiene) have been attracting attention, for example, spiroindane bisoxazoline ligands exhibit excellent asymmetric induction ability in asymmetric insertion reaction of diazocarbene to heteroatom-hydrogen bond. Although the carbon-centered skeleton has been considered as the dominant ligand skeleton, the carbon-centered spirocyclic bisoxazoline does not solve the enantioselectivity problem well in partial reactions. Therefore, the development of a novel spiro-skeleton bisoxazoline ligand has important significance for the development of asymmetric reactions.
Disclosure of Invention
The invention aims to overcome the defect of single type of spirobisdihydrobenzothiole bisoxazoline ligand in the prior art and provides a novel spirobisdihydrobenzothiole bisoxazoline compound, a preparation method and application thereof. The preparation method of the spirobisdihydrobenzothiollo bisoxazoline compound is simple and convenient to operate, and the spirobisdihydrobenzothiollo bisoxazoline compound has excellent asymmetric induction capability or higher asymmetric reaction yield in some asymmetric reactions such as asymmetric insertion reaction of diazocarbene p heteroatom-hydrogen bond.
The present invention solves the above-described problems by the following means.
The invention provides a compound shown as a formula I or a formula II,
wherein R is n1-1 、R n1-2 、R n1-3 、R n1-1’ 、R n1-2’ And R n1-3’ Independently hydrogen, halogen, nitro, C 1 ～C 8 Alkyl radical, C 1 ～C 8 Alkoxy radical, C 1 ～C 8 Alkyl O (C = O) -, C 1 ～C 8 Alkyl (C = O) O-),C 1 ～C 8 Alkyl (C = O) -, C 1 ～C 8 Alkyl (C = O) NH-, [ C = 1 ～C 8 Alkyl (C = O)] 2 N-、R 1-1 R 1-2 R 1-3 Si-、C 6 ～C 15 Aryl radical, by one or more R 1-4 Substituted C 6 ～C 15 Aryl, 5-6 membered heteroaryl with one or more heteroatoms selected from N, O and S and 1-3 heteroatoms or C substituted by one or more halogens 1 ～C 8 An alkyl group; when the substituents are plural, the same or different;
R 2 、R 2’ 、R 3 and R 3’ Independently of one another hydrogen, halogen, C 1 ～C 8 Alkyl radical, C 1 ～C 8 Alkoxy radical, C 1 ～C 8 Alkyl O (C = O) -, C 1 ～C 8 Alkyl (C = O) O-, C 1 ～C 8 Alkyl (C = O) -, C 1 ～C 8 Alkyl (C = O) NH-, [ C { (C) } 1 ～C 8 Alkyl (C = O)] 2 N-、C 6 ～C 15 Aryl, C substituted by one or more halogens 1 ～C 8 Alkyl, by one or more R 2-1 Substituted C 6 ～C 15 Aryl or 5-6 membered heteroaryl with 1-3 heteroatoms selected from one or more of N, O and S; when the substituents are plural, the same or different;
R 1-1 、R 1-2 and R 1-3 Independently is C 1 ～C 8 Alkyl radical, C 1 ～C 8 Alkoxy, phenyl or substituted by one or more R 1-1-1 Substituted phenyl; when the substituents are plural, the same or different;
R 1-4 、R 2-1 and R 1-1-1 Independently of one another, halogen, C 1 ～C 8 Alkyl radical, C 1 ～C 8 Alkoxy radical, C 1 ～C 8 Alkyl O (C = O) -, C 1 ～C 8 Alkyl (C = O) O-, C 1 ～C 8 Alkyl (C = O) -, C 1 ～C 8 Alkyl (C = O) NH-, [ C = 1 ～C 8 Alkyl (C =)O)] 2 N-、R 1 -4-1 R 1-4-2 R 1-4-3 Si-、C 6 ～C 10 Aryl or C substituted by one or more halogens 1 ～C 8 An alkyl group; when the substituents are plural, the same or different;
R 1-4-1 、R 1-4-2 and R 1-4-3 Independently is C 1 ～C 8 Alkyl radical, C 1 ～C 8 Alkoxy or phenyl; when the substituents are plural, the same or different;
“R 2 and R 3 ”、“R 2’ And R 3’ "may also form C independently of the C atom to which it is attached 3 ～C 8 A carbocyclic aliphatic ring, a 3-to 8-membered aliphatic heterocyclic ring with 1 to 3 heteroatoms selected from one or more of N, O and S, or C 6 ～C 10 An aromatic ring;
R 4 、R 4’ 、R 5 、R 5’ 、R 6 、R 6’ 、R 7 、R 7’ 、R 8 、R 8’ 、R 9 and R 9’ Independently of one another hydrogen, halogen, C 1 ～C 8 Alkyl radical, C 1 ～C 8 Alkoxy radical, C 1 ～C 8 Alkyl O (C = O) -, C 1 ～C 8 Alkyl (C = O) O-, C 1 ～C 8 Alkyl (C = O) -, C 1 ～C 8 Alkyl (C = O) NH-, [ C { (C) } 1 ～C 8 Alkyl (C = O)] 2 N-、C 6 ～C 15 Aryl, 5-to 6-membered heteroaryl having one or more heteroatoms selected from N, O and S and 1 to 3 heteroatoms, and R 4-2 R 4-3 R 4-4 C-、C 3 ～C 6 Cycloalkyl radicals, substituted by one or more R a Substituted C 1 ～C 8 Alkyl or by one or more R 4-1 Substituted C 6 ～C 15 An aryl group; when the substituent is plural, it may be the same or different;
“R 4 and R 6 ”、“R 5 And R 6 ”、“R 7 And R 9 ”、“R 8 And R 9 ”、“R 4’ And R 6’ ”、“R 5’ And R 6’ ”、“R 7’ And R 9’ ”、“R 8’ And R 9’ "may also form C independently of the C atom to which it is attached 3 ～C 8 An alicyclic ring, a 3-to 8-membered aliphatic heterocyclic ring with one or more heteroatoms selected from N, O and S, the number of the heteroatoms being 1 to 3, and C 6 ～C 10 Aromatic ring, C 3 ～C 8 Alicyclic ring-on-C 6 ～C 10 Aromatic rings or substituted by one or more R 4-5 Substituted ' heteroatom is selected from one or more of N, O and S, the number of the heteroatom is 1-3 ', and the substituted ' heteroatom is a 3-to 8-membered lipoheterocycle; when the substituents are plural, they may be the same or different;
R a independently halogen or C 6 ～C 10 An aryl group; r is 4-1 、R 4-2 、R 4-3 、R 4-4 And R 4-5 Independently of one another, halogen, C 1 ～C 8 Alkyl radical, C 1 ～C 8 Alkoxy radical, C 1 ～C 8 Alkyl O (C = O) -, C 1 ～C 8 Alkyl (C = O) O-, C 1 ～C 8 Alkyl (C = O) -, C 1 ～C 8 Alkyl (C = O) NH-, [ C = 1 ～C 8 Alkyl (C = O)] 2 N-、R 4-1-1 R 4-1-2 R 4-1-3 Si-, one or more of N, O and S as hetero atom, 5-to 6-membered heteroaryl with 1-3 hetero atoms, and C 6 ～C 15 Aryl, C substituted by one or more halogens 1 ～C 8 Alkyl or by one or more R 4-1-1 Substituted C 6 ～C 15 An aryl group; when the substituent is plural, it may be the same or different;
R 4-1-1 、R 4-1-2 and R 4-1-3 Independently of one another, halogen, C 1 ～C 8 Alkyl radical, C 1 ～C 8 Alkoxy, phenyl or C substituted by one or more halogens 1 ～C 8 An alkyl group;
R 10 and R 10’ Independently a connecting bond, -O-, -S-, -CH 2 -、-CMe 2 -；
* Represents a chiral silicon center which is S-configuration silicon or R-configuration silicon.
In one embodiment, R n1-1 、R n1-2 、R n1-3 、R n1-1’ 、R n1-2’ And R n1-3’ Independently of one another hydrogen, halogen, C 1 ～C 8 Alkyl radical, C 6 ～C 15 Aryl or by one or more R 1-4 Substituted C 6 ～C 15 And (4) an aryl group.
In one embodiment, R 1-4 Independently is C 1 ～C 8 Alkyl radical, C 6 ～C 10 Aryl or C substituted by one or more halogens 1 ～C 8 An alkyl group.
In one embodiment, R 2 、R 2’ 、R 3 And R 3’ Independently of one another is hydrogen, C 1 ～C 8 Alkyl or C 6 ～C 15 And (4) an aryl group.
In one embodiment, R 4 、R 4’ 、R 5 、R 5’ 、R 6 、R 6’ 、R 7 、R 7’ 、R 8 、R 8’ 、R 9 And R 9’ Independently of one another is hydrogen, C 1 ～C 8 Alkyl radical, C 6 ～C 15 Aryl radical, R 4-2 R 4-3 R 4-4 C-、C 3 ～C 6 Cycloalkyl radicals, substituted by one or more R a Substituted C 1 ～C 8 Alkyl or by one or more R 4-1 Substituted C 6 ～C 15 And (3) an aryl group.
In one embodiment, "R" is 4 And R 6 ”、“R 5 And R 6 ”、“R 7 And R 9 ”、“R 8 And R 9 ”、“R 4’ And R 6’ ”、“R 5’ And R 6’ ”、“R 7’ And R 9’ ”、“R 8’ And R 9’ "may also form C independently of the C atom to which it is attached 3 ～C 8 Alicyclic ring, C 3 ～C 8 Carbocyclic aliphatic ring C 6 ～C 10 An aromatic ring, a 3-to 8-membered aliphatic heterocyclic ring containing one or more heteroatoms selected from N, O and S and having 1 to 3 heteroatoms, and one or more R 4-5 The substituted heteroatom is one or more selected from N, O and S, and the number of the heteroatoms is 1-3.
In one embodiment, R 4-1 、R 4-2 、R 4-3 、R 4-4 、R 4-5 Independently of one another is hydrogen, C 1 ～C 8 Alkyl radical, C 1 ～C 8 Alkoxy radical, C 6 ～C 15 Aryl, C substituted by one or more halogens 1 ～C 8 Alkyl or by one or more R 4-1-1 Substituted C 6 ～C 15 And (4) an aryl group.
In one embodiment, R 4-1 Is C 1 ～C 8 Alkoxy or C substituted by one or more halogens 1 ～C 8 An alkyl group.
In one embodiment, R 4-2 And R 4-3 Independently is C 1 ～C 8 Alkyl radical, C 6 ～C 15 Aryl or by one or more R 4 -1-1 Substituted C 6 ～C 15 Aryl, preferably C 1 ～C 8 Alkyl or C 6 ～C 15 And (4) an aryl group.
In one embodiment, R 4-4 Is C 1 ～C 8 Alkyl radical, C 6 ～C 15 Aryl or by one or more R 4-1-1 Substituted C 6 ～C 15 And (3) an aryl group.
In one embodiment, R 4-5 Independently is C 1 ～C 8 An alkyl group.
In one embodiment, R 4-1-1 Is C 1 ～C 8 Alkyl radical, C 1 ～C 8 Alkoxy or C substituted by one or more halogens 1 ～C 8 An alkyl group.
In one embodiment, R n1-1 、R n1-2 、R n1-3 、R n1-1’ 、R n1-2’ And R n1-3’ Independently hydrogen,Halogen, C 1 ～C 8 Alkyl radical, C 6 ～C 15 Aryl radicals or by one or more R 1-4 Substituted C 6 ～C 15 An aryl group;
R 1-4 independently is C 1 ～C 8 Alkyl radical, C 6 ～C 10 Aryl or C substituted by one or more halogens 1 ～C 8 An alkyl group;
R 2 、R 2’ 、R 3 and R 3’ Independently of one another is hydrogen, C 1 ～C 8 Alkyl or C 6 ～C 15 An aryl group;
R 4 、R 4’ 、R 5 、R 5’ 、R 6 、R 6’ 、R 7 、R 7’ 、R 8 、R 8’ 、R 9 and R 9’ Independently of one another is hydrogen, C 1 ～C 8 Alkyl radical, C 6 ～C 15 Aryl radical, R 4-2 R 4-3 R 4-4 C-、C 3 ～C 6 Cycloalkyl radicals, substituted by one or more R a Substituted C 1 ～C 8 Alkyl or by one or more R 4-1 Substituted C 6 ～C 15 An aryl group;
R a independently is C 6 ～C 10 An aryl group;
“R 4 and R 6 ”、“R 5 And R 6 ”、“R 7 And R 9 ”、“R 8 And R 9 ”、“R 4’ And R 6’ ”、“R 5’ And R 6’ ”、“R 7’ And R 9’ ”、“R 8’ And R 9’ "may also form C independently of the C atom to which it is attached 3 ～C 8 Alicyclic ring, C 3 ～C 8 Carbocyclic aliphatic ring C 6 ～C 10 An aromatic ring, a 3-to 8-membered aliphatic heterocyclic ring with one or more heteroatoms selected from N, O and S and 1 to 3 heteroatoms or one or more R 4-5 The substituted heteroatom is one or more selected from N, O and S, and the number of the heteroatoms is 1-3;
R 4-1 、R 4-2 、R 4-3 、R 4-4 、R 4-5 independently of one another is hydrogen, C 1 ～C 8 Alkyl radical, C 1 ～C 8 Alkoxy radical, C 6 ～C 15 Aryl, C substituted by one or more halogens 1 ～C 8 Alkyl or by one or more R 4-1-1 Substituted C 6 ～C 15 An aryl group;
R 4-1-1 is C 1 ～C 8 Alkyl radical, C 1 ～C 8 Alkoxy or C substituted by one or more halogens 1 ～C 8 An alkyl group;
R 10 、R 10’ independently a connecting bond, -O-, -S-or-CH 2 -。
In one embodiment, R n1-1 、R n1-2 、R n1-3 、R n1-1’ 、R n1-2’ And R n1-3’ Independently hydrogen.
In one embodiment, R 2 、R 2’ 、R 3 And R 3’ Independently of one another is hydrogen, C 1 ～C 8 Alkyl or C 6 ～C 15 And (3) an aryl group.
In one embodiment, R 4 、R 4’ 、R 5 、R 5’ 、R 6 、R 6’ 、R 7 、R 7’ 、R 8 、R 8’ 、R 9 And R 9’ Independently of one another is hydrogen, C 1 ～C 8 Alkyl radical, C 6 ～C 15 Aryl radical, C 3 ～C 6 Cycloalkyl radicals or substituted by one or more R a Substituted C 1 ～C 8 An alkyl group.
In one embodiment, R a Independently is C 6 ～C 10 And (3) an aryl group.
In one embodiment, "R" is 4 And R 6 ”、“R 5 And R 6 ”、“R 7 And R 9 ”、“R 8 And R 9 ”、“R 4’ And R 6’ ”、“R 5’ And R 6’ ”、“R 7’ And R 9’ ”、“R 8’ And R 9’ "may also form C independently of the C atom to which it is attached 3 -C 8 Alicyclic ring-on-C 6 ～C 10 An aromatic ring.
In one embodiment, R 10 、R 10’ Independently a connecting bond, -O-, -S-or-CH 2 -。
In one embodiment, R n1-1 、R n1-2 、R n1-3 、R n1-1’ 、R n1-2’ And R n1-3’ Independently is hydrogen;
R 2 、R 2’ 、R 3 and R 3’ Independently H, C 1 ～C 8 Alkyl or C 6 ～C 15 An aryl group;
R 4 、R 4’ 、R 5 、R 5’ 、R 6 、R 6’ 、R 7 、R 7’ 、R 8 、R 8’ 、R 9 and R 9’ Independently of one another is hydrogen, C 1 ～C 8 Alkyl radical, C 6 ～C 15 Aryl radical, C 3 ～C 6 Cycloalkyl radicals or substituted by one or more R a Substituted C 1 ～C 8 An alkyl group;
R a independently is C 6 ～C 10 An aryl group;
“R 4 and R 6 ”、“R 5 And R 6 ”、“R 7 And R 9 ”、“R 8 And R 9 ”、“R 4’ And R 6’ ”、“R 5’ And R 6’ ”、“R 7’ And R 9’ ”、“R 8’ And R 9’ "may also form C independently of the C atom to which it is attached 3 ～C 8 Alicyclic ring-on-C 6 ～C 10 An aromatic ring;
R 10 、R 10’ independently a connecting bond, -O-, -S-or-CH 2 -。
In one embodiment, R 2 And R 2’ Independently is hydrogen or C 1 ～C 8 An alkyl group.
In one embodiment, R 3 And R 3’ Independently hydrogen.
In one embodiment, R 5 、R 5’ 、R 6 、R 6’ 、R 8 、R 8’ 、R 9 And R 9’ Independently hydrogen.
In one embodiment, R 4 、R 4’ 、R 7 And R 7’ Independently is C 1 ～C 8 Alkyl radical, C 6 ～C 15 Aryl or by one or more R a Substituted C 1 ～C 8 An alkyl group.
In one embodiment, R 10 And R 10’ Independently is O.
In one embodiment, R n1-1 、R n1-2 、R n1-3 、R n1-1’ 、R n1-2’ And R n1-3’ Independently is hydrogen;
R 2 and R 2’ Independently hydrogen or C 1 ～C 8 An alkyl group;
R 3 and R 3’ Independently hydrogen;
R 5 、R 5’ 、R 6 、R 6’ 、R 8 、R 8’ 、R 9 and R 9’ Independently is hydrogen;
R 4 、R 4’ 、R 7 and R 7’ Independently is C 1 ～C 8 Alkyl radical, C 6 ～C 15 Aryl radicals or by one or more R a Substituted C 1 ～C 8 An alkyl group;
R a independently is C 6 ～C 10 And (4) an aryl group.
R 10 And R 10’ Independently is O.
In one embodiment, R n1-1 And R n1-1’ The same is true.
In one embodiment, R n1-2 And R n1-2’ The same is true.
In one embodiment, R n1-3 And R n1-3’ The same is true.
In one embodiment, R 2 And R 2’ The same is true.
In one embodiment, R 3 And R 3’ The same is true.
In one embodiment, R 4 And R 4’ The same is true.
In one embodiment, R 5 And R 5’ The same is true.
In one embodiment, R 6 And R 6’ The same is true.
In one embodiment, R 7 And R 7’ The same is true.
In one embodiment, R 8 And R 8’ The same is true.
In one embodiment, R 9 And R 9’ The same is true.
In one embodiment, R 10 And R 10’ The same is true.
In one embodiment, when R n1-1 、R n1-2 、R n1-3 、R n1-1’ 、R n1-2’ And R n1-3’ Independently halogen, the halogen may be fluorine, chlorine, bromine or iodine, preferably chlorine, bromine or iodine.
In one embodiment, when R n1-1 、R n1-2 、R n1-3 、R n1-1’ 、R n1-2’ And R n1-3’ Independently is C 1 ～C 8 Alkyl radical, C 1 ～C 8 Alkyl O (C = O) -, C 1 ～C 8 Alkyl (C = O) O-, C 1 ～C 8 Alkyl (C = O) -, C 1 ～C 8 Alkyl (C = O) NH-or [ C [ ] 1 ～C 8 Alkyl (C = O)] 2 N-is, said C 1 ～C 8 Alkyl groups may independently be methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl or tert-butyl, preferably methyl.
In one embodiment, when R n1-1 、R n1-2 、R n1-3 、R n1-1’ 、R n1-2’ And R n1-3’ Independently is C 1 ～C 8 When alkoxy, said C 1 ～C 8 Alkoxy may be C 1 ～C 4 Alkoxy, for example methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy or tert-butoxy.
In one embodiment, when R n1-1 、R n1-2 、R n1-3 、R n1-1’ 、R n1-2’ And R n1-3’ Independently is C 6 ～C 15 Aryl radicals or by one or more R 1-4 Substituted C 6 ～C 15 When aryl, said C 6 ～C 15 Aryl may independently be C 6 ～C 10 Aryl, preferably phenyl.
In one embodiment, when R n1-1 、R n1-2 、R n1-3 、R n1-1’ 、R n1-2’ And R n1-3’ When the heteroaryl group with 5-6 members is independently selected from one or more of N, O and S, and the number of the heteroatoms is 1-3, the heteroaryl group with 5-6 members can be furyl, thienyl, pyrrolyl or pyridyl.
In one embodiment, when R 2 、R 2’ 、R 3 And R 3’ Independently halogen or C substituted by one or more halogens 1 ～C 8 When alkyl, the halogen may be independently fluorine, chlorine, bromine or iodine.
In one embodiment, when R 2 、R 2’ 、R 3 And R 3’ Independently is C 1 ～C 8 Alkyl radical, C 1 ～C 8 Alkyl O (C = O) -, C 1 ～C 8 Alkyl (C = O) O-, C 1 ～C 8 Alkyl (C = O) -, C 1 ～C 8 Alkyl (C = O) NH-, [ C { (C) } 1 ～C 8 Alkyl (C = O)] 2 N-or C substituted by one or more halogens 1 ～C 8 When alkyl, said C 1 ～C 8 Alkyl groups may independently be methyl, ethyl, propyl, isopropyl, n-butyl, sec-butyl, isobutyl or tert-butylButyl, preferably methyl or ethyl.
In one embodiment, when R 2 、R 2’ 、R 3 And R 3’ Independently is C 6 ～C 15 Aryl radicals or by one or more R 2-1 Substituted C 6 ～C 15 Aryl is said to C 6 ～C 15 Aryl may independently be C 6 ～C 10 Aryl, preferably phenyl.
In one embodiment, when R 2 、R 2’ 、R 3 And R 3’ Independently is C 1 ～C 8 At alkoxy, said C 1 ～C 8 The alkoxy group may be methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy or tert-butoxy.
In one embodiment, when R 2 、R 2’ 、R 3 And R 3’ When the heteroaryl group is a 5-to 6-membered heteroaryl group in which "hetero atom (S) is (are) selected from one or more of N, O and S and the number of hetero atoms is 1 to 3", the 5-to 6-membered heteroaryl group may be independently furyl, thienyl, pyrrolyl or pyridyl.
In one embodiment, when R 1-1 、R 1-2 And R 1-3 Independently is C 1 ～C 8 When alkyl, said C 1 ～C 8 The alkyl group may be methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl or tert-butyl.
In one embodiment, when R 1-1 、R 1-2 And R 1-3 Independently is C 1 ～C 8 When alkoxy, said C 1 ～C 8 The alkoxy group may be methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy or tert-butoxy.
In one embodiment, when R 1-4 、R 2-1 And R 1-1-1 Independently is C 1 ～C 8 Alkyl radical, C 1 ～C 8 Alkyl O (C = O) -, C 1 ～C 8 Alkyl (C = O) O-, C 1 ～C 8 Alkyl (C = O) -, C 1 ～C 8 Alkyl (C = O) NH-, [ C = 1 ～C 8 Alkyl (C = O)] 2 N-or C substituted by one or more halogens 1 ～C 8 When alkyl, said C 1 ～C 8 Alkyl groups may independently be methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl or tert-butyl, preferably methyl or isopropyl.
In one embodiment, when R 1-4 、R 2-1 And R 1-1-1 Independently halogen or C substituted by one or more halogens 1 ～C 8 In the case of alkyl, the halogen may be independently fluorine, chlorine, bromine or iodine, preferably fluorine.
In one embodiment, when R 1-4 、R 2-1 And R 1-1-1 Independently is C 6 ～C 10 When aryl, said C 6 ～C 10 The aryl group can be phenyl.
In one embodiment, when R 1-4-1 、R 1-4-2 And R 1-4-3 Independently is C 1 ～C 8 When alkyl, said C 1 ～C 8 The alkyl group may be methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl or tert-butyl.
In one embodiment, when R 1-4-1 、R 1-4-2 And R 1-4-3 Independently is C 1 ～C 8 At alkoxy, said C 1 ～C 8 The alkoxy group may be methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy or tert-butoxy.
In one embodiment, when "R" is 2 And R 3 ”、“R 2’ And R 3’ "may also form C independently of the C atom to which it is attached 3 ～C 8 When the ring is carbocyclic, said C 3 ～C 8 The carbocyclic aliphatic ring may be cyclopropane, cyclobutane, cyclopentane, or cyclohexane.
In one embodiment, when "R" is 2 And R 3 ”、“R 2’ And R 3’ "may also form, independently from the C atom to which it is attached", a heteroatom selected from one or more of N, O and SWhen the number of hetero atoms is 1 to 3 ", the 3-to 8-membered aliphatic heterocyclic ring may be a 5-to 6-membered aliphatic heterocyclic ring, for example, a tetrahydrofuran ring, a tetrahydropyran ring, a piperidine ring, a morpholine ring or a piperazine ring.
In one embodiment, when "R" is 2 And R 3 ”、“R 2’ And R 3’ "may also form C independently of the C atom to which it is attached 6 ～C 10 When it is an aromatic ring, said C 6 ～C 10 The aromatic ring can be a benzene ring or a naphthalene ring.
In one embodiment, when R 4 、R 4’ 、R 5 、R 5’ 、R 6 、R 6’ 、R 7 、R 7’ 、R 8 、R 8’ 、R 9 And R 9’ Independently is C 1 ～C 8 Alkyl radical, C 1 ～C 8 Alkyl O (C = O) -, C 1 ～C 8 Alkyl (C = O) O-, C 1 ～C 8 Alkyl (C = O) -, C 1 ～C 8 Alkyl (C = O) NH-, [ C { (C) } 1 ～C 8 Alkyl (C = O)] 2 N-or by one or more R a Substituted C 1 ～C 8 When alkyl, said C 1 ～C 8 Alkyl groups may independently be methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl or tert-butyl, preferably methyl, ethyl, isopropyl or tert-butyl, for example methyl, isopropyl or tert-butyl.
In one embodiment, when R 4 、R 4’ 、R 5 、R 5’ 、R 6 、R 6’ 、R 7 、R 7’ 、R 8 、R 8’ 、R 9 And R 9’ Independently halo, the halo can be fluoro, chloro, bromo, or iodo.
In one embodiment, when R 4 、R 4’ 、R 5 、R 5’ 、R 6 、R 6’ 、R 7 、R 7’ 、R 8 、R 8’ 、R 9 And R 9’ Independently C 1 ～C 8 At the time of alkoxySaid C is 1 ～C 8 Alkoxy groups may independently be methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy or tert-butoxy.
In one embodiment, when R 4 、R 4’ 、R 5 、R 5’ 、R 6 、R 6’ 、R 7 、R 7’ 、R 8 、R 8’ 、R 9 And R 9’ Independently is C 6 ～C 15 Aryl radicals or by one or more R 4-1 Substituted C 6 ～C 15 When aryl, said C 6 ～C 15 Aryl may be C 6 ～C 10 Aryl, such as phenyl or naphthyl.
In one embodiment, when R 4 、R 4’ 、R 5 、R 5’ 、R 6 、R 6’ 、R 7 、R 7’ 、R 8 、R 8’ 、R 9 And R 9’ Independently is C 3 ～C 6 When there is a cycloalkyl group, said C 3 ～C 6 Cycloalkyl radicals may be C 5 ～C 6 Cycloalkyl, such as cyclopropyl or cyclohexyl, preferably cyclohexyl.
In one embodiment, when R 4 、R 4’ 、R 5 、R 5’ 、R 6 、R 6’ 、R 7 、R 7’ 、R 8 、R 8’ 、R 9 And R 9’ When the heteroaryl group with 5-6 members is independently 'one or more heteroatoms selected from N, O and S, and the number of the heteroatoms is 1-3', the heteroaryl group with 5-6 members can be furyl, thienyl, pyrrolyl or pyridyl.
In one embodiment, when "R" is 4 And R 6 ”、“R 5 And R 6 ”、“R 7 And R 9 ”、“R 8 And R 9 ”、“R 4’ And R 6’ ”、“R 5’ And R 6’ ”、“R 7’ And R 9’ ”、“R 8’ And R 9’ "independently form with the C atom to which it is attachedC 3 ～C 8 Aliphatic ring, said C 3 ～C 8 The carbocyclic aliphatic ring is independently C 5 ～C 6 Alicyclic rings, such as cyclopentane or cyclohexane.
In one embodiment, when "R" is 4 And R 6 ”、“R 5 And R 6 ”、“R 7 And R 9 ”、“R 8 And R 9 ”、“R 4’ And R 6’ ”、“R 5’ And R 6’ ”、“R 7’ And R 9’ ”、“R 8’ And R 9’ The C atoms connected with the C atoms independently form 3-8 membered lipoheterocycle with heteroatoms selected from one or more of N, O and S and the number of the heteroatoms being 1-3, or one or more R 4-5 When the number of the substituted "hetero atom is 1 to 3" and the number of the hetero atom is one or more of N, O and S, the 3 to 8-membered aliphatic heterocyclic ring is independently "hetero atom is one or more of N, O and S and the number of the hetero atom is 1 to 3" and the number of the hetero atom is 5 to 6-membered aliphatic heterocyclic ring, such as tetrahydrofuran ring, tetrahydropyrrole ring, tetrahydropyran ring, piperidine ring, morpholine ring or piperazine ring.
In one embodiment, when "R" is 4 And R 6 ”、“R 5 And R 6 ”、“R 7 And R 9 ”、“R 8 And R 9 ”、“R 4’ And R 6’ ”、“R 5’ And R 6’ ”、“R 7’ And R 9’ ”、“R 8’ And R 9’ "independently form C with the C atom to which it is attached 3 ～C 8 Alicyclic ring-on-C 6 ～C 10 When it is an aromatic ring, said C 3 ～C 8 The carbocyclic aliphatic ring may be C 5 ～C 6 Alicyclic rings such as cyclopentane; said C 6 ～C 10 The aromatic ring may be a benzene ring or a naphthalene ring, such as a benzene ring; said C 3 ～C 8 Alicyclic ring-on-C 6 ～C 10 The aromatic ring being a cyclopentanobenzene ring, e.g.
In one embodiment, when "R" is 4 And R 6 ”、“R 5 And R 6 ”、“R 7 And R 9 ”、“R 8 And R 9 ”、“R 4’ And R 6’ ”、“R 5’ And R 6’ ”、“R 7’ And R 9’ ”、“R 8’ And R 9’ "independently form C with the C atom to which it is attached 6 ～C 10 When it is an aromatic ring, said C 6 ～C 10 The aromatic ring can be a benzene ring or a naphthalene ring.
In one embodiment, when R a When independently halogen, the halogen may be fluorine, chlorine, bromine or iodine.
In one embodiment, when R a Independently is C 6 ～C 10 Aryl is said to C 6 ～C 10 Aryl may be phenyl or naphthyl, preferably phenyl.
In one embodiment, when R 4-1 、R 4-2 、R 4-3 、R 4-4 And R 4-5 Independently is C 1 ～C 8 Alkyl radical, C 1 ～C 8 Alkyl O (C = O) -, C 1 ～C 8 Alkyl (C = O) O-, C 1 ～C 8 Alkyl (C = O) -, C 1 ～C 8 Alkyl (C = O) NH-, [ C = 1 ～C 8 Alkyl (C = O)] 2 N-or C substituted by one or more halogens 1 ～C 8 When alkyl, said C 1 ～C 8 Alkyl groups may independently be methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl or tert-butyl, preferably methyl.
In one embodiment, when R 4-1 、R 4-2 、R 4-3 、R 4-4 And R 4-5 Independently halogen or C substituted by one or more halogens 1 ～C 8 In the case of alkyl, the halogen may be independently fluorine, chlorine, bromine or iodine, preferably fluorine.
In one embodiment, when R 4-1 、R 4-2 、R 4-3 、R 4-4 And R 4-5 Independently is C 1 ～C 8 When alkoxy, said C 1 ～C 8 The alkoxy group may be methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, sec-butoxy, isobutoxy or tert-butoxy, preferably methoxy.
In one embodiment, when R 4-1 、R 4-2 、R 4-3 、R 4-4 And R 4-5 Independently is C 6 ～C 15 Aryl or by one or more R 4-1-1 Substituted C 6 ～C 15 Aryl is said to C 6 ～C 15 Aryl may be C 6 ～C 10 Aryl, preferably phenyl.
In one embodiment, when R 4-1 、R 4-2 、R 4-3 、R 4-4 And R 4-5 When the heteroaryl group is a 5-to 6-membered heteroaryl group independently having "one or more heteroatoms selected from N, O and S, and the number of heteroatoms being 1 to 3", the 5-to 6-membered heteroaryl group may be furyl, thienyl, pyrrolyl or pyridyl.
In one embodiment, when R 4-1-1 、R 4-1-2 And R 4-1-3 Independently is C 1 ～C 8 Alkyl or C substituted by one or more halogens 1 ～C 8 When alkyl, said C 1 ～C 8 Alkyl groups may independently be methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl or tert-butyl, preferably methyl.
In one embodiment, when R 4-1-1 、R 4-1-2 And R 4-1-3 Independently halogen or C substituted by one or more halogens 1 ～C 8 In the case of alkyl, the halogen may be independently fluorine, chlorine, bromine or iodine, preferably fluorine.
In one embodiment, when R 4-1-1 、R 4-1-2 And R 4-1-3 Independently is C 1 ～C 8 At alkoxy, said C 1 ～C 8 The alkoxy group may be methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, sec-butoxy, isobutoxy or tert-butoxy, preferably methoxy.
In one embodiment, R n1-1 、R n1-2 、R n1-3 、R n1-1’ 、R n1-2’ And R n1-3’ Independently hydrogen, chlorine, bromine, iodine, methyl,
Such as hydrogen.
In one embodiment, R 2 And R 2’ Independently hydrogen, methyl, ethyl or phenyl.
In one embodiment, R 4 、R 4’ 、R 5 、R 5’ 、R 6 、R 6’ 、R 7 、R 7’ 、R 8 、R 8’ 、R 9 And R 9’ Independently hydrogen, methyl, ethyl, isopropyl, tert-butyl,
In one embodiment, "R" is 4 And R 6 ”、“R 5 And R 6 ”、“R 7 And R 9 ”、“R 8 And R 9 ”、“R 4’ And R 6’ ”、“R 5’ And R 6’ ”、“R 7’ And R 9’ ”、“R 8’ And R 9’ "form a C atom attached thereto
In one embodiment, the compound of formula I is a compound of formula Ia, formula Ib, formula Ic, or formula Id;
preferably, in the compounds of formulae Ia, ib, ic and Id, R 3 、R 3’ 、R n1-1 、R n1-1’ 、R n1-2 、R n1-2’ 、R n1-3 And R n1-3’ Are all hydrogen.
It will be understood by those skilled in the art that when the compound of formula I is a compound of formula Ia, formula Ib, formula Ic or formula Id, all of the compounds of formula Ia, formula Ib, formula Ic or formula Id are in a single configuration or predominantly in that configuration.
In one embodiment, the compound of formula Ia is a compound of Ia-1 or Ia-2;
in one embodiment, the compound shown in the formula Ib is a compound shown in Ib-1 or Ib-2;
in one embodiment, the compound of formula Ic is Ic-1 or Ic-2;
in one embodiment, the compound of formula Id is a compound of formula Id-1 or formula Id-2;
in one embodiment, R n1-1 And R n1-1’ Same as R n1-2 And R n1-2’ Same, R n1-3 And R n1-3’ Same as R 2 And R 2’ Same, R 3 And R 3’ The same, and the compound shown in the formula I is selected from any one of the formula Ia-1, ia-2, ib-1, ib-2, ic-1, ic-2, id-1 or Id-2.
In one embodiment, the compound of formula II is a compound of formula IIa or IIb;
it will be understood by those skilled in the art that when the compound of formula II is a compound of formula IIa or IIb, all of the compounds of formula IIa or IIb are in a single configuration or exist in a predominantly favored configuration.
In one embodiment, the compound of formula IIa is a compound of formula IIa-1 or formula IIa-2:
in one embodiment, the compound of formula IIb is a compound of formula IIb-1 or formula IIb-2:
in one embodiment, the compound of formula I or II can be of any of the following structures,
the invention also provides a preparation method of the compound shown as the formula I or the formula II, which is a method 1 or a method 2:
the method 1 comprises the following steps: in an organic solvent, under the action of sulfonyl chloride compounds, alkali and N, N-dimethylamino pyridine, the compound shown in the formula 1 is subjected to intramolecular ring closure reaction shown in the specification;
the method 2 comprises the following steps: in an organic solvent, under the action of sulfonyl chloride compounds, alkali and N, N-dimethylamino pyridine, the compound shown as the formula 2 is subjected to intramolecular ring closure reaction shown as the following formula;
the reaction operations and conditions of the intramolecular ring closure reaction are conventional in the art for such reactions.
In the intramolecular cyclization reaction, the organic solvent can be one or more selected from ether solvents, halogenated hydrocarbon solvents and aromatic solvents. The ether solvent can be one or more selected from tetrahydrofuran, methyl tert-butyl ether, diethyl ether, ethylene glycol dimethyl ether, isopropyl ether, dioxane, n-butyl ether, petroleum ether and n-butyl ether, and is preferably tetrahydrofuran. The halogenated hydrocarbon solvent can be one or more selected from dichloromethane, chloroform and 1, 2-dichloroethane, and dichloromethane is preferred. The aromatic solvent can be one or more selected from toluene, xylene, chlorobenzene and trifluorotoluene, and toluene is preferred.
In the intramolecular ring closure reaction, the organic solvent is a halogenated hydrocarbon solvent, such as dichloromethane.
In the intramolecular ring closure reaction, the alkali can be organic alkali or inorganic alkali. The organic base may be selected from one or more of pyridine, triethylamine, tributylamine, N-methylmorpholine, 1, 8-diazabicyclo [5.4.0] undec-7-ene, 1, 5-diazabicyclo [ 4.3.0 ] non-5-ene, triethylenediamine, N-diisopropylethylamine, N, O-bis (trimethylsilyl) acetamide, N-butyllithium, sec-butyllithium, tert-butyllithium, sodium bis (trimethylsilyl) amide, lithium bis (trimethylsilyl) amide, potassium bis (trimethylsilyl) amide, sodium methoxide, proton sponge, potassium tert-butoxide, and sodium tert-butoxide, preferably triethylamine. The inorganic base may be one or more selected from cesium carbonate, potassium phosphate, potassium acetate, sodium hydride, sodium hydroxide and potassium hydroxide.
In the intramolecular ring closure reaction, the base is the organic base, such as triethylamine.
In the intramolecular ring closure reaction, the sulfonyl chloride compound can be selected from one or more of p-toluenesulfonyl chloride, methanesulfonyl chloride, benzenesulfonyl chloride and p-trifluoromethylbenzenesulfonyl chloride, and is preferably p-toluenesulfonyl chloride and/or methanesulfonyl chloride.
In the intramolecular cyclization reaction, the molar ratio of the compound shown as the formula 1 or the compound shown as the formula 2 to the sulfonyl chloride compound can be 1 (2-6), such as 1.
In the intramolecular cyclization reaction, the molar ratio of the compound shown in the formula 1 or the compound shown in the formula 2 to the alkali can be 1 (2-20), for example, 1.
In the intramolecular cyclization reaction, the molar ratio of the compound shown as the formula 1 or the compound shown as the formula 2 to the N, N-dimethylaminopyridine can be 1 (0.05-0.5), for example, 1.
In one embodiment, in the preparation method, the method 1 may further comprise the following steps: in an organic solvent, under the action of a palladium catalyst, a phosphine ligand and alkali, carrying out amidation reaction shown as the following formula on a compound shown as a formula 3, 2-aminoethanol and CO to obtain a compound shown as a formula 1,
the method 2 can also comprise the following steps: in an organic solvent, under the action of a palladium catalyst, a phosphine ligand and alkali, carrying out amidation reaction shown as the following formula on a compound shown as a formula 4, 2-aminoethanol and CO to obtain a compound shown as a formula 2,
the reaction operations and reaction conditions of the amidation reaction are conventional in the art for such reactions.
In the amidation reaction, the organic solvent may be one or more selected from ether solvents, halogenated hydrocarbon solvents and aromatic solvents. The ether solvent can be one or more selected from tetrahydrofuran, methyl tert-butyl ether, diethyl ether, ethylene glycol dimethyl ether, isopropyl ether, dioxane, n-butyl ether, petroleum ether and n-butyl ether, and is preferably tetrahydrofuran. The halogenated hydrocarbon solvent can be one or more selected from dichloromethane, chloroform and 1, 2-dichloroethane, and dichloromethane is preferred. The aromatic solvent can be one or more selected from toluene, xylene, chlorobenzene and trifluorotoluene, and toluene is preferred.
In one embodiment, in the amidation reaction, the organic solvent is the ether solvent, such as tetrahydrofuran.
In the amidation reaction, the palladium catalyst may be one or more selected from palladium chloride, palladium acetate, tetratriphenylphosphine palladium, bis (triphenylphosphine) palladium dichloride, 1' -bis (diphenylphosphino) ferrocene ] palladium dichloride, bis (dibenzylideneacetone) palladium, bis (tri-tert-butylphosphino) palladium, bis (tricyclohexylphosphine) palladium dichloride, bis [1, 2-bis (diphenylphosphino) ethane ] palladium, tris (dibenzylideneacetone) dipalladium, palladium pivalate, bis (acetonitrile) palladium dichloride, and tetrakis (tri-tert-butylphosphino) palladium and bis (cyanophenyl) palladium dichloride, and is preferably palladium acetate.
In the amidation reaction, the phosphine ligand may be 1, 3-bis (diphenylphosphino) propane.
In the amidation reaction, the base may be an organic base or an inorganic base. The organic base may be selected from one or more of pyridine, triethylamine, tributylamine, N-methylmorpholine, 1, 8-diazabicyclo [5.4.0] undec-7-ene, 1, 5-diazabicyclo [ 4.3.0 ] non-5-ene, triethylenediamine, N-diisopropylethylamine, N, O-bis (trimethylsilyl) acetamide, N-butyllithium, sec-butyllithium, tert-butyllithium, sodium bis (trimethylsilyl) amide, lithium bis (trimethylsilyl) amide, potassium bis (trimethylsilyl) amide, sodium methoxide, proton sponge, potassium tert-butoxide, and sodium tert-butoxide. The inorganic base may be one or more selected from cesium carbonate, potassium phosphate, potassium acetate, sodium hydride, sodium hydroxide and potassium hydroxide.
In the amidation reaction, the base may be the above-mentioned organic base, for example, triethylamine.
In the amidation reaction, the pressure of the CO is 1 to 10bar, for example 2bar.
In the amidation reaction, the molar ratio of the compound shown as the formula 3 or the compound shown as the formula 4 to the 2-aminoethanol can be 1 (2-6), such as 1.
In the amidation reaction, the molar ratio of the compound shown as the formula 3 or the compound shown as the formula 4 to the palladium catalyst can be 1 (0.05-0.2), for example, 1.
In the amidation reaction, the molar ratio of the compound shown as the formula 3 or the compound shown as the formula 4 to the phosphine ligand can be 1 (0.05-0.2), for example, 1.
In the amidation reaction, the molar ratio of the compound shown as the formula 3 or the compound shown as the formula 4 to the base can be 1 (3-7), for example, 1.
The reaction temperature of the amidation reaction may be 30 to 120 ℃, for example, 90 ℃.
In one embodiment, in the preparation method, the method 1 may further comprise the following steps: in an organic solvent, under the action of alkali, the compound shown as the formula 5 and a trifluoromethanesulfonylation reagent are subjected to trifluoromethanesulfonic acid esterification reaction shown as the following to obtain a compound shown as the formula 3,
the method 2 can also comprise the following steps: in an organic solvent, under the action of alkali, the compound shown as the formula 6 and a trifluoromethanesulfonylation reagent are subjected to trifluoromethanesulfonic acid esterification reaction shown as the following to obtain a compound shown as the formula 4,
the reaction conditions and operation of the triflation reaction described are conventional in the art for such reactions.
In the triflate esterification reaction, the organic solvent can be one or more selected from ether solvents, halogenated hydrocarbon solvents and aromatic solvents. The ether solvent can be one or more selected from tetrahydrofuran, methyl tert-butyl ether, diethyl ether, ethylene glycol dimethyl ether, isopropyl ether, dioxane, n-butyl ether, petroleum ether and n-butyl ether, and is preferably tetrahydrofuran. The halogenated hydrocarbon solvent can be one or more selected from dichloromethane, chloroform and 1, 2-dichloroethane, and dichloromethane is preferred. The aromatic solvent can be one or more selected from toluene, xylene, chlorobenzene and trifluorotoluene, and toluene is preferred.
In one embodiment, the organic solvent in the triflation reaction is the halogenated hydrocarbon solvent, such as methylene chloride.
In the triflation esterification reaction, the triflation reagent can be trifluoromethanesulfonic anhydride.
In the triflation esterification reaction, the alkali can be organic alkali or inorganic alkali. The organic base may be selected from one or more of pyridine, triethylamine, tributylamine, N-methylmorpholine, 1, 8-diazabicyclo [5.4.0] undec-7-ene, 1, 5-diazabicyclo [ 4.3.0 ] non-5-ene, triethylenediamine, N-diisopropylethylamine, N, O-bis (trimethylsilyl) acetamide, N-butyllithium, sec-butyllithium, tert-butyllithium, sodium bis (trimethylsilyl) amide, lithium bis (trimethylsilyl) amide, potassium bis (trimethylsilyl) amide, sodium methoxide, proton sponge, potassium tert-butoxide, and sodium tert-butoxide. The inorganic base can be one or more of cesium carbonate, potassium phosphate, potassium acetate, sodium hydride, sodium hydroxide and potassium hydroxide.
In one embodiment, the base in the triflation reaction is the organic base, such as triethylamine and/or pyridine.
In the triflate esterification reaction, the molar ratio of the compound shown as the formula 5 or the compound shown as the formula 6 to the triflate reagent can be 1 (2-6), for example, 1.
In the triflate esterification reaction, the molar ratio of the compound shown as the formula 5 or the compound shown as the formula 6 to the alkali can be 1 (2-6), for example, 1.
The invention also provides a compound shown as the formula 1 or the formula 2.
In one embodiment, the compound of formula 1 or formula 2 is:
the invention provides a catalyst composition which comprises a metal complex formed by a compound X and a salt of a metal in a third group to a thirteenth group and/or a mixture (in-situ mixture) of the compound X and a reagent of the metal in the third group to the thirteenth group, wherein the compound X is a compound shown as the formula I or the formula II. Wherein said third to thirteenth groups mean columns 3 to 13 of the periodic Table of the elements. The metal reagent is a complex of metal center and other atoms in covalent bond, such as bis (tri-tert-butylphosphine) palladium or ferrocene.
In one embodiment, the group iii to thirteenth metals may be those conventional in the art, such as Cu, fe, or Pd; the salt of the group III to thirteenth metals may be Cu (MeCN) 4 PF 6 、Fe(OTf) 2 、Pd(PhCN) 2 Cl 2 。
The molar ratio of said compound X to said group iii to thirteenth metal in said catalyst composition may be any molar ratio conventional in the art, such as 1.
In one embodiment, the catalytic composition comprises a metal complex of a compound of formula I as described above with a salt of a metal of the third to thirteenth groups and/or a mixture (in situ mixture) of a compound of formula I as described above with a reagent of a metal of the third to thirteenth groups.
The invention also provides application of the compound shown as the formula I, the compound shown as the formula II or the catalyst composition in catalysis of asymmetric organic synthesis reaction, wherein the organic synthesis reaction is an insertion reaction of carbene to a phenol O-H bond and/or an insertion reaction of para-amine N-H bond.
In one embodiment, the organic synthesis reaction is a palladium-catalyzed insertion of a carbene p-phenol O-H bond and/or a copper-catalyzed insertion of a carbene p-amine N-H bond. Preferably, the carbene is prepared from diazophenylacetate.
In one embodiment, the application is scheme one or scheme two:
the first scheme comprises the following steps: in an organic solvent, in the presence of a palladium catalyst, the compound shown in the formula I or the formula II and a coordination salt, carrying out an insertion reaction shown in the following on the compound shown in the formula VI and the compound shown in the formula VII to obtain the compound shown in the formula VIIa or the formula VIIb;
the second scheme comprises the following steps: in an organic solvent, in the presence of a copper catalyst, a coordination salt and the compound shown in the formula I or the formula II, carrying out an insertion reaction shown in the following on the compound shown in the formula VI and the compound shown in the formula VIII to obtain the compound shown in the formula VIIIa or the formula VIIIb;
wherein R in the first scheme and the second scheme is C 1 ～C 6 Alkyl or benzyl, such as methyl, ethyl, tert-butyl, isopropyl or benzyl;
In the first and second schemes, the reaction operation and conditions of the insertion reaction may be conventional in the art for such insertion reactions.
In the first scheme, in the insertion reaction, when the compound shown in the formula I is the compound shown in the formula Ia or Ic, the compound shown in the formula VIIa is obtained; and when the compound shown in the formula I is a compound shown in a formula Ib or Id, obtaining a compound shown in a formula VIIb. Preferably, the compound shown in formula Ia is a compound shown in formula Ia-1, such as
Preferably, the compound shown in the formula Ib is a compound shown in a formula Ib-2, such as
In the first scheme, in the insertion reaction, when the compound shown in the formula II is the compound shown in the formula IIa, the compound shown in the formula VIIa is obtained; when the compound shown in the formula II is the compound shown in the formula IIb, the compound shown in the formula VIIb is obtained. Preferably, the compound of formula IIa is a compound of formula IIa-1, e.g. is
Preferably, the compound of formula IIb is a compound of formula IIb-2, e.g.
In one embodiment, the insertion reaction in the first embodiment may be carried out in the presence of an inert gas, which may be an inert gas commonly used in the art for such reactions, such as nitrogen and/or argon.
In one embodiment, the insertion reaction in the first embodiment can be carried out under anhydrous conditions, preferably, the anhydrous conditions are achieved by adding molecular sieves to the reaction system, which molecular sieves can be conventional in the art, such as, for example, molecular sieves used in such reactions
Molecular sieves or
Molecular sieves, preferably
A molecular sieve; the mass molar ratio of the molecular sieve to the compound shown in the formula VI can be 0.1g to 1g, for example, 0.5g.
In the first aspect, the
Independently is unsubstituted or Ar 1-1 Substituted C 6 ～C 15 Aryl or unsubstituted 5-to 6-membered heteroaryl with one or more heteroatoms selected from N, O and S, and 1 to 3 heteroatoms, preferably unsubstituted or Ar 1-1 Substituted C 6 ～C 15 An aryl group; ar (Ar) 1-1 Is amino, halogen, C 1 ～C 8 Alkyl, halo C 1 ～C 8 Alkyl radical, C 6 ～C 15 Aryl radical, C 1 ～C 8 Alkoxy or C 1 ～C 8 alkyl-O (C = O) -, preferably halogen, C 1 ～C 8 Alkyl or C 6 ～C 15 And (3) an aryl group.
In one embodiment, in the first aspect, the
Is composed of
In one embodiment, in the first aspect, the
Is composed of
In the first embodiment, in the insertion reaction, the organic solvent may be a halogenated hydrocarbon solvent, such as one or more selected from dichloromethane, chloroform, 1, 2-dichloroethane, 1, 2-tetrachloroethane and carbon tetrachloride, preferably dichloromethane.
In the first embodiment, in the insertion reaction, the palladium catalyst may be one or more selected from palladium chloride, palladium acetate, tetratriphenylphosphine palladium, bis (triphenylphosphine) palladium dichloride, 1' -bis (diphenylphosphino) ferrocene ] palladium dichloride, bis (dibenzylideneacetone) palladium, bis (tri-tert-butylphosphino) palladium, bis (tricyclohexylphosphine) palladium dichloride, bis [1, 2-bis (diphenylphosphino) ethane ] palladium, tris (dibenzylideneacetone) dipalladium, palladium pivalate, bis (acetonitrile) palladium dichloride, tetrakis (tri-tert-butylphosphino) palladium and bis (cyanophenyl) palladium dichloride, and is preferably bis (cyanophenyl) palladium dichloride.
In the first embodiment, the coordination salt in the insertion reaction may be selected from one or more of sodium tetrakis (3, 5-bis (trifluoromethyl) phenyl) borate, silver hexafluoroantimonate, silver tetrafluoroborate and silver bistrifluoromethanesulfonylimide, and is preferably sodium tetrakis (3, 5-bis (trifluoromethyl) phenyl) borate.
In the first scheme, in the insertion reaction, the molar ratio of the palladium catalyst to the compound shown in formula VI can be 1.
In the first scheme, in the insertion reaction, the molar ratio of the compound shown in formula I or formula II to the compound shown in formula VI can be 1-1.
In the first scheme, in the insertion reaction, the molar ratio of the coordination salt to the compound shown in formula VI can be 1.
In the first embodiment, in the insertion reaction, the molar ratio of the compound represented by the formula VII to the compound represented by the formula VI may be 0.5.
In the first scheme, in the insertion reaction, the molar concentration of the compound shown in the formula VI in the organic solvent can be 0.05-0.5mol/L, for example 0.2mol/L.
In the first embodiment, the temperature of the insertion reaction may be-10-110 deg.C, for example, 20-40 deg.C.
In the first embodiment, the reaction time of the insertion reaction is such that the reactants are completely reacted or no longer reacted, for example, 0.2 to 48 hours.
In the second scheme, in the insertion reaction, when the compound shown in the formula I is the compound shown in the formula Ia or Ic, the compound shown in the formula VIIIa is obtained; when the compound shown in the formula I is a compound shown in the formula Ib or Id, the compound shown in the formula VIIIb is obtained. Preferably, the compound of formula Ia is a compound of formula Ia-1, e.g.
Preferably, the compound shown in the formula Ib is a compound shown in a formula Ib-2, such as
In the second scheme, in the insertion reaction, when the formula IIWhen the compound is a compound shown in a formula IIa, a compound shown in a formula VIIIa is obtained; when the compound shown in the formula II is the compound shown in the formula IIb, the compound shown in the formula VIIIb is obtained. Preferably, the compound of formula IIa is a compound of formula IIa-1, for example
Preferably, the compound of formula IIb is a compound of formula IIb-2, e.g.
In one embodiment, in the second embodiment, the insertion reaction may be performed in the presence of an inert gas, which may be an inert gas commonly used in the art for such reactions, such as nitrogen and/or argon.
In one embodiment, the insertion reaction in the second embodiment can be carried out under anhydrous conditions, preferably, the anhydrous conditions are achieved by adding molecular sieves, which are conventional in the art, such as
Molecular sieves or
Molecular sieves, preferably
A molecular sieve; the mass mol ratio of the molecular sieve to the compound shown in the formula VI can be 0.1g to 11g, such as 0.5g.
In one embodiment, the second embodiment is the same as the first embodiment
Independently is unsubstituted C 6 ～C 15 Aryl radicals, for example phenyl.
In the second scheme, in the insertion reaction, the organic solvent may be a halogenated hydrocarbon solvent, such as one or more selected from dichloromethane, chloroform, 1, 2-dichloroethane, 1, 2-tetrachloroethane and carbon tetrachloride, preferably dichloromethane.
In the second scheme, in the insertion reaction, the copper catalyst may be one or more selected from cuprous chloride, cuprous bromide, cuprous iodide, cuprous cyanide, tetraacetonitrileconium hexafluorophosphate, tetraacetonitrileconium tetrafluoroborate, cuprous bromide dimethylsulfide complex, cuprous hexafluorophosphate, cuprous toluene trifluoromethanesulfonate complex, cuprous benzene trifluoromethanesulfonate complex, cupric chloride, cupric bromide, cupric sulfate, cupric perchlorate, bis (trifluoromethanesulfonyl) imide copper and cupric trifluoromethanesulfonate; preferably tetraacetonitrileconpper hexafluorophosphate.
In the second embodiment, in the insertion reaction, the complex salt may be selected from one or more of sodium tetrakis (3, 5-bis (trifluoromethyl) phenyl) borate, silver hexafluoroantimonate, silver tetrafluoroborate and silver bistrifluoromethanesulfonylimide, and preferably sodium tetrakis (3, 5-bis (trifluoromethyl) phenyl) borate.
In the second scheme, in the insertion reaction, the molar ratio of the copper catalyst to the compound represented by the formula VI can be 1.
In the second scheme, in the insertion reaction, the molar ratio of the compound represented by formula I or formula II to the compound represented by formula VI may be 1.
In the second scheme, in the insertion reaction, the molar ratio of the coordination salt to the compound represented by the formula VI can be 1.
In the second scheme, in the insertion reaction, the molar ratio of the compound shown in formula VIII to the compound shown in formula VI can be from 0.5.
In the second scheme, in the insertion reaction, the molar concentration of the compound shown in formula VI in the organic solvent may be 0.05-0.5mol/L, for example, 0.2mol/L.
In the second embodiment, the temperature of the insertion reaction may be-10 to 70 ℃, for example, 20 to 40 ℃.
In the second embodiment, the reaction time of the insertion reaction is such that the reactants are completely reacted or no longer reacted, for example, 0.2 to 48 hours.
The term "halogen" refers to fluorine, chlorine, bromine or iodine.
The term "alkyl" refers to a radical having the indicated number of carbon atoms (e.g., C) 1 ～C 8 ) A linear or branched, saturated monovalent hydrocarbon group. Alkyl groups include, but are not limited to: methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, n-hexyl, and the like.
The term "alkoxy" refers to the group R X -O-，R X Is as defined for the term "alkyl". Alkoxy groups include, but are not limited to: methoxy, ethoxy, n-propoxy, isopropoxy, and the like.
The term "aryl" refers to a group having the indicated number of carbon atoms (e.g., C) 6 ～C 15 ) And (2) a cyclic, unsaturated monovalent hydrocarbon group which is monocyclic or polycyclic (for example, 2 or 3), and in which when polycyclic, two atoms and a bond are shared between monocyclic rings, and each ring has aromatic properties. The aryl group is attached to the rest of the molecule through a carbon atom in the aromatic ring. Aryl groups include, but are not limited to: phenyl or naphthyl, and the like.
The term "heteroaryl" refers to a cyclic, unsaturated, monovalent group of a specified heteroatom species (one or more of N, O, and S) having a specified number of ring atoms (e.g., 5 to 6 members), a specified number of heteroatoms (e.g., 1,2, or 3), and having aromatic character. The heteroaryl group is attached to the rest of the molecule through a carbon or heteroatom.
The term "cycloalkyl" refers to a ring having the indicated number of carbon atoms (e.g., C) 3 ～C 6 ) A cyclic, saturated monovalent hydrocarbon group. Cycloalkyl groups include, but are not limited to:
and so on.
The term "alicyclic ring" satisfies any one of the following conditions, and the remainder is defined as the term "cycloalkyl": 1. linked to the rest of the molecule by more than two single bonds; 2. sharing two atoms and one bond with the rest of the molecule.
The term "heterocycloaliphatic" has a cyclic, saturated ring of a specified heteroatom species (one or more of N, O and S) with a specified number of ring atoms (e.g., 3 to 8 members), a specified number of heteroatoms (e.g., 1,2, or 3), which satisfies any of the following conditions: 1. linked to the rest of the molecule by more than two single bonds; 2. sharing two atoms and one bond with the rest of the molecule.
The term "aromatic ring" satisfies any of the following conditions, with the remainder being defined as the term "aryl": 1. linked to the rest of the molecule by more than two single bonds; 2. sharing two atoms and one bond with the rest of the molecule.
On the basis of the common knowledge in the field, the above preferred conditions can be combined randomly to obtain the preferred embodiments of the invention.
The reagents and starting materials used in the present invention are commercially available.
The positive progress effects of the invention are as follows:
(1) The invention provides a spiro-bis-dihydrobenzothiollo-bis-oxazoline compound with a novel structure, which shows excellent asymmetric induction capability or enables the yield of the involved asymmetric reaction to be higher in some asymmetric reactions such as asymmetric insertion reaction of diazo-carbene p-heteroatom-hydrogen bond.
(2) The preparation method of the spirobisdihydrobenzothiollo bisoxazoline compound provided by the invention is simple and convenient to operate and has high yield.
Detailed Description
The invention is further illustrated by the following examples, which are not intended to limit the scope of the invention. The experimental methods without specifying specific conditions in the following examples were selected according to the conventional methods and conditions, or according to the commercial instructions.
Example 1: synthesis of Compound I-b
After adding II-1 (296mg, 1mmol) to a 25mL dry Schlenk tube and displacing nitrogen, DCM and pyridine (0.19mL, 2.3mmol) were added, tf was added dropwise under cooling with an ice-water bath 2 O (0.42mL, 2.5mmol). After the addition was complete, the mixture was stirred at room temperature, monitored by TLC until I-a disappeared completely, and then saturated NaHCO was used 3 (aq) quench reaction, extract with DCM, combine organic phases with Na 2 SO 4 After drying, the solvent was removed under reduced pressure and the crude product was isolated by column chromatography (PE: EA = 20).
Example 2: synthesis of Compound I-1c
To a 20mL dry sample tube, I-b (561mg, 1mmol), pd (OAc) were added 2 (11.2mg, 0.05mmol), dppp (24.7 mg), aminoalcohol (412mg, 4 mmol), then placed in an autoclave, nitrogen replaced, 5mL THF and E addedt 3 After N (0.69mL, 5 mmol), the autoclave was charged with CO three times and the pressure adjusted to 2bar and then at 90 ℃. After 24h, the system was filtered and the solvent was removed directly under reduced pressure, and the crude product was isolated by column chromatography (PE: EA =1 2) to give 303mg of a white solid in 69% yield.
I-1c
Example 3: synthesis of spirobisdihydrobenzothiollo bisoxazoline I-1
IV (421mg, 1.0mmol), tsCl (4.0 equiv), DMAP (20 mol%) were put into a 25mL Schlenk tube, nitrogen was purged, DCM was added to a concentration of about 0.05M, and the system was cooled in an ice-water bath, et was added 3 After N (20 equiv), the system was slowly returned to room temperature. The reaction was monitored by TLC and, after completion of the reaction, saturated NaHCO was used 3 (aq) quenching reaction, extracting the aqueous phase with DCM, combining the organic phases, drying by spinning, and separating the crude product by column chromatography to obtain the bisoxazoline product, wherein the yield of the bisoxazoline product is 347mg and 86% of white solid.
The following preparation method of the compound shown in the formula II is similar to the preparation method of the compound I-1 shown in the formula I, and only the compound skeleton and the substituent of the non-reactive site are correspondingly replaced.
Application example 1 (ligand screening): palladium catalyzes the asymmetric insertion reaction of diazophenylacetate carbene with respect to the phenol O-H bond.
General reaction operation: adding PdCl under the protection of nitrogen 2 (PhCN) 2 (19.2mg, 0.05mmol), spirodihydrobenzothiolol bisoxazoline ligand (0.06 mmol), sodium tetrakis (3, 5-bis (trifluoromethyl) phenyl) borate (106.3mg, 0.12mmol),
MS (500 mg) then 5mL CH 2 Cl 2 . After 2 hours, phenol (141.1mg, 1.5mmol) was added, stirring was carried out at room temperature, and then 5mL of CH was added with methyl diazophenylacetate (176mg, 1.0mmol) using a syringe pump 2 Cl 2 The solution was dropped into the above reaction system for a total dropping time of 1 hour. After the dropwise addition, stirring is kept at room temperature until the TLC tracking reaction is complete, then the reaction system is filtered by silica gel, the solvent is removed by reduced pressure distillation, and the product IV is obtained by thin layer chromatography separation (n-hexane/ethyl acetate: 20/1). The ee value of the product was determined by HPLC. In contrast to the examples in the prior art using spiroindane bisoxazoline (Angew. Chem. Int. Ed.2014,53, 2978-2981), when I-27 is used as a ligand, it is possible to useHigher yields and comparable ee values were obtained.
TABLE 1 ligand screening
Application example 2 (substrate extension): palladium catalyzes the asymmetric insertion reaction of diazophenylacetate carbene on a phenol O-H bond.
Adding PdCl under the protection of nitrogen 2 (PhCN) 2 (19.2mg, 0.05mmol), spirodihydrobenzothiollobisoxazoline ligand (33.3mg, 0.06mmol), sodium tetrakis (3, 5-bis (trifluoromethyl) phenyl) borate (106.3mg, 0.12mmol),
MS (500 mg) then 5mL CH 2 Cl 2 . After 2 hours, phenol (1.5 mmol) was added, stirring at room temperature, then methyl diazophenylacetate (176mg, 1.0 mmol) was placed in 5mL CH using a syringe pump 2 Cl 2 The solution was dropped into the above reaction system for a total dropping time of 1 hour. After the dropwise addition was completed, stirring was maintained at room temperature until the TLC-follow-up reaction was completed, then the reaction system was filtered with silica gel, the solvent was removed by distillation under reduced pressure, and thin layer chromatography (n-hexane/ethyl acetate: 20/1) was carried out to obtain product IV. The ee value of the product was determined by HPLC. Product configuration reference (Angew. Chem. Int. Ed.2014,53, 2978-2981).
IV-1:
IV-2:
IV-3:
IV-4:
IV-5:
Application example 3 (ligand screening): palladium catalyzes the asymmetric insertion reaction of diazophenylacetate carbene para-aniline N-H bond.
Adding Cu (MeCN) under the protection of nitrogen 4 PF 6 (18.6mg, 0.05mmol), spirodihydrobenzothiollobisoxazoline ligand (33.3mg, 0.06mmol), sodium tetrakis (3, 5-bis (trifluoromethyl) phenyl) borate (106.3mg, 0.12mmol),
MS (500 mg) then 5mL CH 2 Cl 2 . After 2 hours, phenol (1.5 mmol) was added, stirring at room temperature, and then methyl diazophenylacetate (176mg, 1.0 mmol) was added to 5mL CH using a syringe pump 2 Cl 2 The solution was dropped into the above reaction system for a total dropping time of 1 hour. After the dropwise addition, stirring is kept at room temperature until the TLC tracking reaction is complete, then the reaction system is filtered by silica gel, the solvent is removed by reduced pressure distillation, and the product IV is obtained by thin layer chromatography separation (n-hexane/ethyl acetate: 20/1). The ee value of the product was determined by HPLC. Product configuration reference (j.am. Chem. Soc.2007,129, 5834).
TABLE 2 ligand screening
Claims (19)
1. A compound as shown in formula I or II,
wherein R is n1-1 、R n1-2 、R n1-3 、R n1-1’ 、R n1-2’ And R n1-3’ Independently hydrogen, halogen, nitro, C 1 ～C 8 Alkyl radical, C 1 ～C 8 Alkoxy radical, C 1 ～C 8 Alkyl O (C = O) -, C 1 ～C 8 Alkyl (C = O) O-, C 1 ～C 8 Alkyl (C = O) -, C 1 ～C 8 Alkyl (C = O) NH-, [ C = 1 ～C 8 Alkyl (C = O)] 2 N-、R 1-1 R 1-2 R 1-3 Si-、C 6 ～C 15 Aryl radical, by one or more R 1-4 Substituted C 6 ～C 15 Aryl, 5-6 membered heteroaryl with one or more heteroatoms selected from N, O and S and 1-3 heteroatoms or C substituted by one or more halogens 1 ～C 8 An alkyl group; when the substituents are plural, the same or different;
R 2 、R 2’ 、R 3 and R 3’ Independently of one another hydrogen, halogen, C 1 ～C 8 Alkyl radical, C 1 ～C 8 Alkoxy radical, C 1 ～C 8 Alkyl O (C = O) -, C 1 ～C 8 Alkyl (C = O) O-, C 1 ～C 8 Alkyl (C = O) -, C 1 ～C 8 Alkyl (C = O) NH-, [ C = 1 ～C 8 Alkyl (C = O)] 2 N-、C 6 ～C 15 Aryl, C substituted by one or more halogens 1 ～C 8 Alkyl, by one or more R 2-1 Substituted C 6 ～C 15 Aryl, orA 5-6 membered heteroaryl group in which "hetero atom (S) is (are) selected from one or more of N, O and S, and the number of hetero atoms is 1-3"; when the substituents are plural, the same or different;
R 1-1 、R 1-2 and R 1-3 Independently is C 1 ～C 8 Alkyl radical, C 1 ～C 8 Alkoxy, phenyl or substituted by one or more R 1-1-1 Substituted phenyl; when the substituents are plural, the same or different;
R 1-4 、R 2-1 and R 1-1-1 Independently of one another is halogen, C 1 ～C 8 Alkyl radical, C 1 ～C 8 Alkoxy radical, C 1 ～C 8 Alkyl O (C = O) -, C 1 ～C 8 Alkyl (C = O) O-, C 1 ～C 8 Alkyl (C = O) -, C 1 ～C 8 Alkyl (C = O) NH-, [ C = 1 ～C 8 Alkyl (C = O)] 2 N-、R 1-4-1 R 1 -4-2 R 1-4-3 Si-、C 6 ～C 10 Aryl or C substituted by one or more halogens 1 ～C 8 An alkyl group; when the substituents are plural, the same or different;
R 1-4-1 、R 1-4-2 and R 1-4-3 Independently is C 1 ～C 8 Alkyl radical, C 1 ～C 8 Alkoxy or phenyl; when the substituents are plural, the same or different;
“R 2 and R 3 ”、“R 2’ And R 3’ "may also form C independently of the C atom to which it is attached 3 ～C 8 A carbocyclic aliphatic ring, a 3-to 8-membered aliphatic heterocyclic ring with 1 to 3 heteroatoms selected from one or more of N, O and S, or C 6 ～C 10 An aromatic ring;
R 4 、R 4’ 、R 5 、R 5’ 、R 6 、R 6’ 、R 7 、R 7’ 、R 8 、R 8’ 、R 9 and R 9’ Independently of one another hydrogen, halogen, C 1 ～C 8 Alkyl radical, C 1 ～C 8 Alkoxy radical, C 1 ～C 8 Alkyl radicalO(C＝O)-、C 1 ～C 8 Alkyl (C = O) O-, C 1 ～C 8 Alkyl (C = O) -, C 1 ～C 8 Alkyl (C = O) NH-, [ C = 1 ～C 8 Alkyl (C = O)] 2 N-、C 6 ～C 15 Aryl, 5-to 6-membered heteroaryl having one or more heteroatoms selected from N, O and S and 1 to 3 heteroatoms, and R 4-2 R 4-3 R 4-4 C-、C 3 ～C 6 Cycloalkyl radicals, substituted by one or more R a Substituted C 1 ～C 8 Alkyl or by one or more R 4-1 Substituted C 6 ～C 15 An aryl group; when the substituents are plural, the same or different;
“R 4 and R 6 ”、“R 5 And R 6 ”、“R 7 And R 9 ”、“R 8 And R 9 ”、“R 4’ And R 6’ ”、“R 5’ And R 6’ ”、“R 7’ And R 9’ ”、“R 8’ And R 9’ "may also form C independently of the C atom to which it is attached 3 ～C 8 A carbocyclic aliphatic ring, a 3-to 8-membered aliphatic heterocyclic ring containing 1 to 3 heteroatoms selected from one or more of N, O and S, and C 6 ～C 10 Aromatic ring, C 3 ～C 8 Carbocyclic aliphatic ring C 6 ～C 10 Aromatic rings or substituted by one or more R 4-5 The substituted heteroatom is one or more selected from N, O and S, and the number of the heteroatoms is 1-3; when the substituents are plural, the same or different;
R a independently halogen or C 6 ～C 10 An aryl group; r is 4-1 、R 4-2 、R 4-3 、R 4-4 And R 4-5 Independently of one another, halogen, C 1 ～C 8 Alkyl radical, C 1 ～C 8 Alkoxy radical, C 1 ～C 8 Alkyl O (C = O) -, C 1 ～C 8 Alkyl (C = O) O-, C 1 ～C 8 Alkyl (C = O) -, C 1 ～C 8 Alkyl (C = O) NH-, [ C { (C) } 1 ～C 8 Alkyl (C = O)] 2 N-、R 4-1-1 R 4-1-2 R 4-1-3 Si-, one or more heteroatoms selected from N, O and S, 5-to 6-membered heteroaryl with 1-3 heteroatoms, and C 6 ～C 15 Aryl, C substituted by one or more halogens 1 ～C 8 Alkyl or by one or more R 4-1-1 Substituted C 6 ～C 15 An aryl group; when the substituents are plural, the same or different;
R 4-1-1 、R 4-1-2 and R 4-1-3 Independently of one another, halogen, C 1 ～C 8 Alkyl radical, C 1 ～C 8 Alkoxy, phenyl or C substituted by one or more halogens 1 ～C 8 An alkyl group;
R 10 and R 10’ Independently a connecting bond, -O-, -S-, -CH 2 -、-CMe 2 -；
* Represents a chiral silicon center which is S-configuration silicon or R-configuration silicon.
2. A compound of formula I or formula II according to claim 1, which satisfies one or more of the following conditions:
(1)R n1-1 、R n1-2 、R n1-3 、R n1-1’ 、R n1-2’ and R n1-3’ Independently of one another hydrogen, halogen, C 1 ～C 8 Alkyl radical, C 6 ～C 15 Aryl radicals or by one or more R 1-4 Substituted C 6 ～C 15 An aryl group;
(2)R 1-4 independently is C 1 ～C 8 Alkyl radical, C 6 ～C 10 Aryl or C substituted by one or more halogens 1 ～C 8 An alkyl group;
(3)R 2 、R 2’ 、R 3 and R 3’ Independently of one another is hydrogen, C 1 ～C 8 Alkyl or C 6 ～C 15 An aryl group;
(4)R 4 、R 4’ 、R 5 、R 5’ 、R 6 、R 6’ 、R 7 、R 7’ 、R 8 、R 8’ 、R 9 and R 9’ Independently of one another is hydrogen, C 1 ～C 8 Alkyl radical, C 6 ～C 15 Aryl radical, R 4 -2 R 4-3 R 4-4 C-、C 3 ～C 6 Cycloalkyl radicals, substituted by one or more R a Substituted C 1 ～C 8 Alkyl or by one or more R 4-1 Substituted C 6 ～C 15 An aryl group; "R 4 And R 6 ”、“R 5 And R 6 ”、“R 7 And R 9 ”、“R 8 And R 9 ”、“R 4’ And R 6’ ”、“R 5’ And R 6’ ”、“R 7’ And R 9’ ”、“R 8’ And R 9’ "may also form C independently of the C atom to which it is attached 3 ～C 8 Alicyclic ring, C 3 ～C 8 Carbocyclic aliphatic ring C 6 ～C 10 An aromatic ring, a 3-to 8-membered aliphatic heterocyclic ring containing one or more heteroatoms selected from N, O and S and having 1 to 3 heteroatoms, and one or more R 4-5 The substituted heteroatom is one or more selected from N, O and S, and the number of the heteroatoms is 1-3;
(5)R 4-1 、R 4-2 、R 4-3 、R 4-4 、R 4-5 independently of one another is hydrogen, C 1 ～C 8 Alkyl radical, C 1 ～C 8 Alkoxy radical, C 6 ～C 15 Aryl, C substituted by one or more halogens 1 ～C 8 Alkyl or by one or more R 4-1-1 Substituted C 6 ～C 15 An aryl group; preferably, R 4-1 Is C 1 ～C 8 Alkoxy or C substituted by one or more halogens 1 ～C 8 An alkyl group; preferably, R 4-2 And R 4-3 Independently is C 1 ～C 8 Alkyl radical, C 6 ～C 15 Aryl radicals or by one or more R 4-1-1 Substituted C 6 ～C 15 Aryl, preferably C 1 ～C 8 Alkyl or C 6 ～C 15 An aryl group; preferably, R 4-4 Is C 1 ～C 8 Alkyl radical, C 6 ～C 15 Aryl or by one or more R 4-1-1 Substituted C 6 ～C 15 An aryl group; preferably, R 4-5 Independently is C 1 ～C 8 An alkyl group;
(6)R 4-1-1 is C 1 ～C 8 Alkyl radical, C 1 ～C 8 Alkoxy or C substituted by one or more halogens 1 ～C 8 An alkyl group.
3. A compound of formula I or formula II according to claim 2, which satisfies one or more of the following conditions:
(1)R n1-1 、R n1-2 、R n1-3 、R n1-1’ 、R n1-2’ and R n1-3’ Independently hydrogen;
(2)R 2 、R 2’ 、R 3 and R 3’ Independently of one another is hydrogen, C 1 ～C 8 Alkyl or C 6 ～C 15 An aryl group;
(3)R 4 、R 4’ 、R 5 、R 5’ 、R 6 、R 6’ 、R 7 、R 7’ 、R 8 、R 8’ 、R 9 and R 9’ Independently of one another is hydrogen, C 1 ～C 8 Alkyl radical, C 6 ～C 15 Aryl radical, C 3 ～C 6 Cycloalkyl radicals or substituted by one or more R a Substituted C 1 ～C 8 An alkyl group; "R 4 And R 6 ”、“R 5 And R 6 ”、“R 7 And R 9 ”、“R 8 And R 9 ”、“R 4’ And R 6’ ”、“R 5’ And R 6’ ”、“R 7’ And R 9’ ”、“R 8’ And R 9’ "may also form C independently of the C atom to which it is attached 3 -C 8 Carbocyclic aliphatic ring C 6 ～C 10 Aromatic rings
(4)R a Independently is C 6 ～C 10 An aryl group;
(5)R 10 、R 10’ independently a connecting bond, -O-, -S-or-CH 2 -。
4. A compound according to claim 3, of formula I or II, wherein one or more of the following conditions is satisfied:
(1)R 2 and R 2’ Independently hydrogen or C 1 ～C 8 An alkyl group;
(2)R 3 and R 3’ Independently hydrogen;
(3)R 5 、R 5’ 、R 6 、R 6’ 、R 8 、R 8’ 、R 9 and R 9’ Independently is hydrogen;
(4)R 4 、R 4’ 、R 7 and R 7’ Independently is C 1 ～C 8 Alkyl radical, C 6 ～C 15 Aryl or by one or more R a Substituted C 1 ～C 8 An alkyl group;
(5)R 10 and R 10’ Independently is O.
5. A compound of formula I or formula II according to claim 4, which satisfies one or more of the following conditions:
(1)R n1-1 and R n1-1’ The same;
(2)R n1-2 and R n1-2’ The same;
(3)R n1-3 and R n1-3’ The same;
(4)R 2 and R 2’ The same;
(5)R 3 and R 3’ The same;
(6)R 4 and R 4’ The same;
(7)R 5 and R 5’ The same;
(8)R 6 and R 6’ The same;
(9)R 7 and R 7’ The same;
(10)R 8 and R 8’ The same;
(11)R 9 and R 9’ The same;
(12)R 10 and R 10’ The same is true.
6. A compound of formula I or formula II according to claim 5, which satisfies one or more of the following conditions:
(1) When R is n1-1 、R n1-2 、R n1-3 、R n1-1’ 、R n1-2’ And R n1-3’ When independently halogen, said halogen is fluorine, chlorine, bromine or iodine, preferably chlorine, bromine or iodine;
(2) When R is n1-1 、R n1-2 、R n1-3 、R n1-1’ 、R n1-2’ And R n1-3’ Independently is C 1 ～C 8 Alkyl radical, C 1 ～C 8 Alkyl O (C = O) -, C 1 ～C 8 Alkyl (C = O) O-, C 1 ～C 8 Alkyl (C = O) -, C 1 ～C 8 Alkyl (C = O) NH-or [ C [ ] 1 ～C 8 Alkyl (C = O)] 2 N-is, said C 1 ～C 8 Alkyl is independently methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl or tert-butyl, preferably methyl;
(3) When R is n1-1 、R n1-2 、R n1-3 、R n1-1’ 、R n1-2’ And R n1-3’ Independently is C 1 ～C 8 At alkoxy, said C 1 ～C 8 Alkoxy is C 1 ～C 4 Alkoxy, such as methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy or tert-butoxy;
(4) When R is n1-1 、R n1-2 、R n1-3 、R n1-1’ 、R n1-2’ And R n1-3’ Independently is C 6 ～C 15 Aryl radicals or by one or more R 1-4 Substituted C 6 ～C 15 Aryl is said to C 6 ～C 15 Aryl is independently C 6 ～C 10 Aryl, preferably phenyl;
(5) When R is n1-1 、R n1-2 、R n1-3 、R n1-1’ 、R n1-2’ And R n1-3’ When the heteroaryl is 5-6-membered heteroaryl, the heteroatom is one or more selected from N, O and S, and the number of the heteroatoms is 1-3, the 5-6-membered heteroaryl is furyl, thienyl, pyrrolyl or pyridyl;
(6) When R is 2 、R 2’ 、R 3 And R 3’ Independently halogen or C substituted by one or more halogens 1 ～C 8 When alkyl, said halogen is independently fluorine, chlorine, bromine or iodine;
(7) When R is 2 、R 2’ 、R 3 And R 3’ Independently is C 1 ～C 8 Alkyl radical, C 1 ～C 8 Alkyl O (C = O) -, C 1 ～C 8 Alkyl (C = O) O-, C 1 ～C 8 Alkyl (C = O) -, C 1 ～C 8 Alkyl (C = O) NH-, [ C { (C) } 1 ～C 8 Alkyl (C = O)] 2 N-or C substituted by one or more halogens 1 ～C 8 When alkyl, said C 1 ～C 8 Alkyl is independently methyl, ethyl, propyl, isopropyl, n-butyl, sec-butyl, isobutyl or tert-butyl, preferably methyl or ethyl;
(8) When R is 2 、R 2’ 、R 3 And R 3’ Independently is C 6 ～C 15 Aryl radicals or by one or more R 2-1 Substituted C 6 ～C 15 When aryl, said C 6 ～C 15 Aryl is independently C 6 ～C 10 Aryl, preferably phenyl;
(9) When R is 2 、R 2’ 、R 3 And R 3’ Independently is C 1 ～C 8 At alkoxy, said C 1 ～C 8 Alkoxy is methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy or tert-butoxy;
(10) When R is 2 、R 2’ 、R 3 And R 3’ When the heteroaryl is 5-6-membered heteroaryl, the heteroatom is one or more selected from N, O and S, and the number of heteroatoms is 1-3, the 5-6-membered heteroaryl is independently furyl, thienyl, pyrrolyl or pyridyl;
(11) When R is 1-1 、R 1-2 And R 1-3 Independently is C 1 ～C 8 When alkyl, said C 1 ～C 8 Alkyl is methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl or tert-butyl;
(12) When R is 1-1 、R 1-2 And R 1-3 Independently is C 1 ～C 8 At alkoxy, said C 1 ～C 8 Alkoxy is methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy or tert-butoxy;
(13) When R is 1-4 、R 2-1 And R 1-1-1 Independently is C 1 ～C 8 Alkyl radical, C 1 ～C 8 Alkyl O (C = O) -, C 1 ～C 8 Alkyl (C = O) O-, C 1 ～C 8 Alkyl (C = O) -, C 1 ～C 8 Alkyl (C = O) NH-, [ C = 1 ～C 8 Alkyl (C = O)] 2 N-or C substituted by one or more halogens 1 ～C 8 When alkyl, said C 1 ～C 8 Alkyl is independently methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl or tert-butyl, preferably methyl or isopropyl;
(14) When R is 1-4 、R 2-1 And R 1-1-1 Independently halogen or C substituted by one or more halogens 1 ～C 8 When alkyl, said halogen is independently fluorine, chlorine, bromine or iodine, preferably fluorine;
(15) When R is 1-4 、R 2-1 And R 1-1-1 Independently is C 6 ～C 10 When aryl, said C 6 ～C 10 Aryl is phenyl;
(16) When R is 1-4-1 、R 1-4-2 And R 1-4-3 Independently is C 1 ～C 8 When alkyl, said C 1 ～C 8 Alkyl is methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl or tert-butyl;
(17) When R is 1-4-1 、R 1-4-2 And R 1-4-3 Independently is C 1 ～C 8 At alkoxy, said C 1 ～C 8 Alkoxy is methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy or tert-butoxy;
(18) When "R" is 2 And R 3 ”、“R 2’ And R 3’ "independently form C with the C atom to which it is attached 3 ～C 8 When the ring is carbocyclic, said C 3 ～C 8 The alicyclic ring is cyclopropane, cyclobutane, cyclopentane or cyclohexane;
(19) When "R" is 2 And R 3 ”、“R 2’ And R 3’ "independently form" a 3-to 8-membered aliphatic heterocyclic ring in which the hetero atom is one or more selected from the group consisting of N, O and S and the number of hetero atoms is 1 to 3 ", the 3-to 8-membered aliphatic heterocyclic ring is a 5-to 6-membered aliphatic heterocyclic ring, for example, a tetrahydrofuran ring, a tetrahydropyrrole ring, a piperidine ring, a morpholine ring or a piperazine ring;
(20) When "R" is 2 And R 3 ”、“R 2’ And R 3’ "independently form C with the C atom to which it is attached 6 ～C 10 When it is an aromatic ring, said C 6 ～C 10 The aromatic ring is a benzene ring or a naphthalene ring;
(21) When R is 4 、R 4’ 、R 5 、R 5’ 、R 6 、R 6’ 、R 7 、R 7’ 、R 8 、R 8’ 、R 9 And R 9’ Independently is C 1 ～C 8 Alkyl radical, C 1 ～C 8 Alkyl O (C = O) -, C 1 ～C 8 Alkyl (C = O) O-, C 1 ～C 8 Alkyl (C = O) -, C 1 ～C 8 Alkyl (C = O) NH-, [ C = 1 ～C 8 Alkyl (C = O)] 2 N-or by one or more R a Substituted C 1 ～C 8 When alkyl, said C 1 ～C 8 Alkyl is independently methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl or tert-butyl, preferably methyl, ethyl, isopropyl or tert-butyl, for example methyl, isopropyl or tert-butyl;
(22) When R is 4 、R 4’ 、R 5 、R 5’ 、R 6 、R 6’ 、R 7 、R 7’ 、R 8 、R 8’ 、R 9 And R 9’ Independently halo, said halo is fluoro, chloro, bromo, or iodo;
(23) When R is 4 、R 4’ 、R 5 、R 5’ 、R 6 、R 6’ 、R 7 、R 7’ 、R 8 、R 8’ 、R 9 And R 9’ Independently C 1 ～C 8 When alkoxy, said C 1 ～C 8 Alkoxy is independently methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, or tert-butoxy;
(24) When R is 4 、R 4’ 、R 5 、R 5’ 、R 6 、R 6’ 、R 7 、R 7’ 、R 8 、R 8’ 、R 9 And R 9’ Independently is C 6 ～C 15 Aryl or by one or more R 4-1 Substituted C 6 ～C 15 Aryl is said to C 6 ～C 15 Aryl is C 6 ～C 10 Aryl, such as phenyl or naphthyl;
(25) When R is 4 、R 4’ 、R 5 、R 5’ 、R 6 、R 6’ 、R 7 、R 7’ 、R 8 、R 8’ 、R 9 And R 9’ Independently is C 3 ～C 6 When there is a cycloalkyl group, said C 3 ～C 6 Cycloalkyl being C 5 ～C 6 Cycloalkyl, such as cyclopropyl or cyclohexyl, preferably cyclohexyl;
(26) When R is 4 、R 4’ 、R 5 、R 5’ 、R 6 、R 6’ 、R 7 、R 7’ 、R 8 、R 8’ 、R 9 And R 9’ When the heteroatom is 5-6 membered heteroaryl with one or more heteroatoms selected from N, O and S and the number of heteroatoms is 1-3, the 5-6 membered heteroaryl is furyl, thienyl, pyrrolyl or pyridyl;
(27) When is "R 4 And R 6 ”、“R 5 And R 6 ”、“R 7 And R 9 ”、“R 8 And R 9 ”、“R 4’ And R 6’ ”、“R 5’ And R 6’ ”、“R 7’ And R 9’ ”、“R 8’ And R 9’ "independently form C with the C atom to which it is attached 3 ～C 8 When the ring is carbocyclic, said C 3 ～C 8 The carbocyclic aliphatic ring is independently C 5 ～C 6 Alicyclic rings such as cyclopentane or cyclohexane;
(28) When is "R 4 And R 6 ”、“R 5 And R 6 ”、“R 7 And R 9 ”、“R 8 And R 9 ”、“R 4’ And R 6’ ”、“R 5’ And R 6’ ”、“R 7’ And R 9’ ”、“R 8’ And R 9’ The C atoms connected with the C atoms independently form 3-8 membered lipoheterocycle with heteroatoms selected from one or more of N, O and S and the number of the heteroatoms being 1-3, or one or more R 4-5 When the substituted "hetero atom is one or more selected from N, O and S and the number of hetero atoms is 1 to 3", the 3 to 8-membered aliphatic heterocyclic ring is independently one or more "hetero atoms selected from N, O and S and the number of hetero atoms is 1 to 3", and the substituted "hetero atom is a 5 to 6-membered aliphatic heterocyclic ring such as a tetrahydrofuran ring, a tetrahydropyrrole ring, a piperidine ring, a morpholine ring or a piperazine ring;
(29) When is "R 4 And R 6 ”、“R 5 And R 6 ”、“R 7 And R 9 ”、“R 8 And R 9 ”、“R 4’ And R 6’ ”、“R 5’ And R 6’ ”、“R 7’ And R 9’ ”、“R 8’ And R 9’ "independently form C with the C atom to which it is attached 3 ～C 8 Carbocyclic aliphatic ring C 6 ～C 10 When it is an aromatic ring, said C 3 ～C 8 The carbocyclic aliphatic ring being C 5 ～C 6 Alicyclic rings such as cyclopentane; said C 6 ～C 10 The aromatic ring is preferably a benzene ring or a naphthalene ring, such as a benzene ring; preferably, said C 3 ～C 8 Carbocyclic aliphatic ring C 6 ～C 10 The aromatic ring being a cyclopentanobenzene ring, e.g.
(30) When "R" is 4 And R 6 ”、“R 5 And R 6 ”、“R 7 And R 9 ”、“R 8 And R 9 ”、“R 4’ And R 6’ ”、“R 5’ And R 6’ ”、“R 7’ And R 9’ ”、“R 8’ And R 9’ "independently form C with the C atom to which it is attached 6 ～C 10 When it is an aromatic ring, said C 6 ～C 10 The aromatic ring is a benzene ring or a naphthalene ring;
(31) When R is a When independently halogen, said halogen is fluorine, chlorine, bromine or iodine;
(32) When R is a Independently is C 6 ～C 10 Aryl is said to C 6 ～C 10 Aryl is phenyl or naphthyl, preferably phenyl;
(33) When R is 4-1 、R 4-2 、R 4-3 、R 4-4 And R 4-5 Independently is C 1 ～C 8 Alkyl radical, C 1 ～C 8 Alkyl O (C = O) -, C 1 ～C 8 Alkyl (C = O) O-, C 1 ～C 8 Alkyl (C = O) -, C 1 ～C 8 Alkyl (C = O) NH-, [ C { (C) } 1 ～C 8 Alkyl (C = O)] 2 N-or C substituted by one or more halogens 1 ～C 8 When alkyl, said C 1 ～C 8 Alkyl is independently methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl or tert-butyl, preferably methyl;
(34) When R is 4-1 、R 4-2 、R 4-3 、R 4-4 And R 4-5 Independently halogen or C substituted by one or more halogens 1 ～C 8 When alkyl, said halogen is independently fluorine, chlorine, bromine or iodine, preferably fluorine;
(35) When R is 4-1 、R 4-2 、R 4-3 、R 4-4 And R 4-5 Independently is C 1 ～C 8 When alkoxy, said C 1 ～C 8 Alkoxy is methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, sec-butoxy, isobutoxy or tert-butoxy, preferably methoxy;
(36) When R is 4-1 、R 4-2 、R 4-3 、R 4-4 And R 4-5 Independently is C 6 ～C 15 Aryl radicals or by one or more R 4-1-1 Substituted C 6 ～C 15 When aryl, said C 6 ～C 15 Aryl is C 6 ～C 10 Aryl, preferably phenyl;
(37) When R is 4-1 、R 4-2 、R 4-3 、R 4-4 And R 4-5 When the heteroaryl is 5-6-membered heteroaryl with one or more heteroatoms selected from N, O and S and 1-3 heteroatoms independently, the 5-6-membered heteroaryl is furyl, thienyl, pyrrolyl or pyridyl;
(38) When R is 4-1-1 、R 4-1-2 And R 4-1-3 Independently is C 1 ～C 8 Alkyl or C substituted by one or more halogens 1 ～C 8 When alkyl, said C 1 ～C 8 Alkyl is independently methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl or tert-butyl, preferably methyl;
(39) When R is 4-1-1 、R 4-1-2 And R 4-1-3 Independently halogen or substituted by one or moreHalogen substituted C 1 ～C 8 When alkyl, said halogen is independently fluorine, chlorine, bromine or iodine, preferably fluorine;
(40) When R is 4-1-1 、R 4-1-2 And R 4-1-3 Independently is C 1 ～C 8 When alkoxy, said C 1 ～C 8 Alkoxy is methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, sec-butoxy, isobutoxy or tert-butoxy, preferably methoxy.
7. A compound of formula I or formula II according to claim 1, which satisfies one or more of the following conditions:
(1)R n1-1 、R n1-2 、R n1-3 、R n1-1’ 、R n1-2’ and R n1-3’ Independently hydrogen, chlorine, bromine, iodine, methyl,
Such as hydrogen;
(2)R 2 and R 2’ Independently hydrogen, methyl, ethyl or phenyl;
(3)R 4 、R 4’ 、R 5 、R 5’ 、R 6 、R 6’ 、R 7 、R 7’ 、R 8 、R 8’ 、R 9 and R 9’ Independently hydrogen, methyl, ethyl, isopropyl, tert-butyl,
(4)“R 4 And R 6 ”、“R 5 And R 6 ”、“R 7 And R 9 ”、“R 8 And R 9 ”、“R 4’ And R 6’ ”、“R 5’ And R 6’ ”、“R 7’ And R 9’ ”、“R 8’ And R 9’ "form a C atom attached thereto
8. The compound of formula I or formula II according to any one of claims 1 to 7, wherein the compound of formula I is a compound of formula Ia, formula Ib, formula Ic or formula Id:
preferably, in the compounds of formulae Ia, ib, ic and Id, R 3 、R 3’ 、R n1-1 、R n1-1’ 、R n1-2 、R n1-2’ 、R n1-3 And R n1-3’ Are all hydrogen;
the compound shown in the formula II is a compound shown in a formula IIa or IIb;
9. the compound of formula I or formula II as claimed in claim 8 wherein the compound of formula Ia is a compound of formula Ia-1 or Ia-2:
the compound shown in the formula Ib is a compound shown in Ib-1 or Ib-2:
the compound shown in the formula Ic is a compound shown as Ic-1 or Ic-2:
the compound shown in the formula Id is a compound shown in a formula Id-1 or a formula Id-2:
the compound shown in the formula IIa is a compound shown in the formula IIa-1 or the formula IIa-2:
the compound shown in the formula IIb is a compound shown in a formula IIb-1 or a formula IIb-2:
10. the compound of formula I or formula II according to claim 9, wherein the compound of formula I or II is of any one of the following structures,
11. a process for the preparation of a compound of formula I or formula II according to any one of claims 1 to 10, which is process 1 or process 2:
the method 1 comprises the following steps: in an organic solvent, under the action of sulfonyl chloride compounds, alkali and N, N-dimethylamino pyridine, the compound shown in the formula 1 is subjected to intramolecular ring closure reaction shown in the specification;
the method 2 comprises the following steps: in an organic solvent, under the action of sulfonyl chloride compounds, alkali and N, N-dimethylamino pyridine, the compound shown as the formula 2 is subjected to intramolecular ring closure reaction shown as the following formula;
preferably, the intramolecular ring closure reaction satisfies one or more of the following conditions:
(1) The organic solvent is selected from one or more of ether solvents, halogenated hydrocarbon solvents and aromatic solvents; preferably, the ether solvent is one or more selected from tetrahydrofuran, methyl tert-butyl ether, diethyl ether, ethylene glycol dimethyl ether, isopropyl ether, dioxane, n-butyl ether, petroleum ether and n-butyl ether, and is preferably tetrahydrofuran; preferably, the halogenated hydrocarbon solvent is selected from one or more of dichloromethane, chloroform and 1, 2-dichloroethane, preferably dichloromethane; preferably, the aromatic solvent is selected from one or more of toluene, xylene, chlorobenzene and trifluorotoluene, and is preferably toluene;
(2) The alkali is organic alkali or inorganic alkali; preferably, the organic base is selected from one or more of pyridine, triethylamine, tributylamine, N-methylmorpholine, 1, 8-diazabicyclo [5.4.0] undec-7-ene, 1, 5-diazabicyclo [ 4.3.0 ] non-5-ene, triethylenediamine, N-diisopropylethylamine, N, O-bis (trimethylsilyl) acetamide, N-butyllithium, sec-butyllithium, tert-butyllithium, sodium bis (trimethylsilyl) amide, lithium bis (trimethylsilyl) amide, potassium bis (trimethylsilyl) amide, sodium methoxide, proton sponge, potassium tert-butoxide, and sodium tert-butoxide, preferably triethylamine; preferably, the inorganic base is one or more selected from cesium carbonate, potassium phosphate, potassium acetate, sodium hydride, sodium hydroxide and potassium hydroxide;
(3) The sulfonyl chloride compound is selected from one or more of paratoluensulfonyl chloride, methanesulfonyl chloride, benzenesulfonyl chloride and p-trifluoromethylbenzenesulfonyl chloride, and is preferably paratoluensulfonyl chloride and/or methanesulfonyl chloride;
(4) The molar ratio of the compound shown as the formula 1 or the compound shown as the formula 2 to the sulfonyl chloride compound is 1 (2-6), such as 1;
(5) The mol ratio of the compound shown in the formula 1 or the compound shown in the formula 2 to the alkali is 1 (2-20), such as 1;
(6) The molar ratio of the compound shown as the formula 1 or the compound shown as the formula 2 to the N, N-dimethylamino pyridine is 1 (0.05-0.5), such as 1.
12. A process for the preparation of a compound of formula I or formula II according to claim 11, wherein:
the method 1 further comprises the following steps: in an organic solvent, under the action of a palladium catalyst, a phosphine ligand and alkali, carrying out amidation reaction shown as the following formula 3 on a compound shown as the formula 3, 2-aminoethanol and CO to obtain a compound shown as the formula 1,
the method 2 further comprises the following steps: in an organic solvent, under the action of a palladium catalyst, a phosphine ligand and alkali, carrying out amidation reaction shown as the following formula on a compound shown as a formula 4, 2-aminoethanol and CO to obtain a compound shown as a formula 2,
preferably, the amidation reaction satisfies one or more of the following conditions:
(1) The organic solvent is selected from one or more of ether solvents, halogenated hydrocarbon solvents and aromatic solvents; preferably, the ether solvent is one or more selected from tetrahydrofuran, methyl tert-butyl ether, diethyl ether, ethylene glycol dimethyl ether, isopropyl ether, dioxane, n-butyl ether, petroleum ether and n-butyl ether, and is preferably tetrahydrofuran; preferably, the halogenated hydrocarbon solvent is selected from one or more of dichloromethane, chloroform and 1, 2-dichloroethane, preferably dichloromethane; preferably, the aromatic solvent is selected from one or more of toluene, xylene, chlorobenzene and trifluorotoluene, and is preferably toluene;
(2) The palladium catalyst is selected from one or more of palladium chloride, palladium acetate, tetratriphenylphosphine palladium, bis (triphenylphosphine) palladium dichloride, 1' -bis (diphenylphosphino) ferrocene palladium dichloride, bis (dibenzylideneacetone) palladium, bis (tri-tert-butylphosphino) palladium, bis (tricyclohexylphosphine) palladium dichloride, bis [1, 2-bis (diphenylphosphino) ethane ] palladium, tris (dibenzylideneacetone) dipalladium, palladium pivalate, bis (acetonitrile) palladium dichloride and tetrakis (tri-tert-butylphosphino) palladium dichloride and bis (cyanophenyl) palladium dichloride, and is preferably palladium acetate;
(3) The phosphine ligand is 1, 3-bis (diphenylphosphino) propane;
(4) The alkali is organic alkali or inorganic alkali; preferably, the organic base is selected from one or more of pyridine, triethylamine, tributylamine, N-methylmorpholine, 1, 8-diazabicyclo [5.4.0] undec-7-ene, 1, 5-diazabicyclo [ 4.3.0 ] non-5-ene, triethylenediamine, N-diisopropylethylamine, N, O-bis (trimethylsilyl) acetamide, N-butyllithium, sec-butyllithium, tert-butyllithium, sodium bis (trimethylsilyl) amide, lithium bis (trimethylsilyl) amide, potassium bis (trimethylsilyl) amide, sodium methoxide, proton sponge, potassium tert-butoxide, and sodium tert-butoxide; preferably, the inorganic base is one or more selected from cesium carbonate, potassium phosphate, potassium acetate, sodium hydride, sodium hydroxide and potassium hydroxide;
(5) The pressure of the CO is 1-10 bar, such as 2bar;
(6) The molar ratio of the compound shown as the formula 3 or the compound shown as the formula 4 to the 2-aminoethanol is 1 (2-6), such as 1;
(7) The molar ratio of the compound shown as the formula 3 or the compound shown as the formula 4 to the palladium catalyst is 1 (0.05-0.2), such as 1;
(8) The molar ratio of the compound shown as the formula 3 or the compound shown as the formula 4 to the phosphine ligand is 1 (0.05-0.2), such as 1;
(9) The mol ratio of the compound shown as the formula 3 or the compound shown as the formula 4 to the alkali is 1 (3-7), such as 1;
(10) The reaction temperature of the amidation reaction is 30 to 120 ℃, for example, 90 ℃.
13. A process for the preparation of a compound of formula I or formula II according to claim 12, wherein:
the method 1 further comprises the following steps: in an organic solvent, under the action of alkali, the compound shown as the formula 5 and a trifluoromethanesulfonylation reagent are subjected to trifluoromethanesulfonic acid esterification reaction shown as the following to obtain a compound shown as the formula 3,
the method 2 further comprises the following steps: in an organic solvent, under the action of alkali, the compound shown as the formula 6 and a trifluoromethanesulfonylation reagent are subjected to trifluoromethanesulfonic acid esterification reaction shown as the following to obtain a compound shown as the formula 4,
preferably, the triflation reaction satisfies one or more of the following conditions:
(1) The organic solvent is selected from one or more of ether solvents, halogenated hydrocarbon solvents and aromatic solvents; preferably, the ether solvent is one or more selected from tetrahydrofuran, methyl tert-butyl ether, diethyl ether, ethylene glycol dimethyl ether, isopropyl ether, dioxane, n-butyl ether, petroleum ether and n-butyl ether, and is preferably tetrahydrofuran; preferably, the halogenated hydrocarbon solvent is selected from one or more of dichloromethane, chloroform and 1, 2-dichloroethane, preferably dichloromethane; preferably, the aromatic solvent is selected from one or more of toluene, xylene, chlorobenzene and trifluorotoluene, and is preferably toluene;
(2) The trifluoromethanesulfonylation reagent is trifluoromethanesulfonic anhydride;
(3) The alkali is organic alkali or inorganic alkali; preferably, the organic base is selected from one or more of pyridine, triethylamine, tributylamine, N-methylmorpholine, 1, 8-diazabicyclo [5.4.0] undec-7-ene, 1, 5-diazabicyclo [ 4.3.0 ] non-5-ene, triethylenediamine, N-diisopropylethylamine, N, O-bis (trimethylsilyl) acetamide, N-butyllithium, sec-butyllithium, tert-butyllithium, sodium bis (trimethylsilyl) amide, lithium bis (trimethylsilyl) amide, potassium bis (trimethylsilyl) amide, sodium methoxide, proton sponge, potassium tert-butoxide, and sodium tert-butoxide; preferably, the inorganic base is one or more selected from cesium carbonate, potassium phosphate, potassium acetate, sodium hydride, sodium hydroxide and potassium hydroxide;
(4) The molar ratio of the compound shown as the formula 5 or the compound shown as the formula 6 to the trifluoromethanesulfonylation reagent is 1 (2-6), such as 1;
(5) The molar ratio of the compound shown as the formula 5 or the compound shown as the formula 6 to the alkali is 1 (2-6), such as 1.
14. A compound of formula 1 or formula 2:
wherein each substituent is as defined in any one of claims 1 to 10;
preferably, the compound represented by formula 1 or formula 2 is any one of the following compounds:
15. a catalyst composition comprising a metal complex of compound X with a salt of a group iii to thirteenth metal and/or a mixture (in situ mixture) of compound X with a group iii to thirteenth metal reagent, said compound X being a compound of formula I or formula II as claimed in any one of claims 1 to 10;
preferably, the catalyst composition satisfies one or more of the following conditions:
(1) The third to thirteenth group metals are Cu, fe or Pd;
(2) The salt of a metal of the third to thirteenth groups is Cu (MeCN) 4 PF 6 、Fe(OTf) 2 、Pd(PhCN) 2 Cl 2 ；
(3) The molar ratio of said compound X to said group iii to thirteenth metals is 1 to 4, for example 1.2;
(4) The compound X is a compound shown in the formula I as claimed in any one of claims 1 to 10.
16. Use of a compound of formula I according to any one of claims 1 to 10, a compound of formula II or a catalyst composition according to claim 15 in the catalysis of asymmetric organic synthesis reactions, said organic synthesis reactions being the insertion reaction of carbene to a phenol O-H bond and/or the insertion reaction of a para-amine N-H bond;
preferably, the organic synthesis reaction is an insertion reaction of carbene p-phenol O-H bond catalyzed by a palladium catalyst and/or an insertion reaction of carbene p-amine N-H bond catalyzed by a copper catalyst; preferably, the carbene is prepared from diazophenylacetate.
17. The use of claim 16, wherein the use is scheme one or scheme two:
the first scheme comprises the following steps: in an organic solvent, in the presence of a palladium catalyst, a compound shown as a formula I or a formula II and a coordination salt, carrying out an insertion reaction shown as the following formula on a compound shown as a formula VI and a compound shown as a formula VII to obtain a compound shown as a formula VIIa or a formula VIIb;
the second scheme comprises the following steps: in an organic solvent, in the presence of a copper catalyst, coordination salt and a compound shown as a formula I or a formula II, carrying out an insertion reaction shown as the following on a compound shown as a formula VI and a compound shown as a formula VIII to obtain a compound shown as a formula VIIIa or a formula VIIIb;
wherein R in the first scheme and the second scheme is C 1 ～C 6 Alkyl or benzyl, such as methyl, ethyl, tert-butyl, isopropyl or benzyl;
18. Use according to claim 17, characterized in that it satisfies one or more of the following conditions:
(1) In the first scheme and the second scheme, the insertion reaction is carried out in the presence of inert gas, such as nitrogen and/or argon;
(2) In the first scheme and the second scheme, the insertion reaction is carried out under anhydrous conditions; preferably, the anhydrous condition is realized by adding molecular sieve into the reaction system, and the anhydrous condition is realized by adding molecular sieve into the reaction systemThe molecular sieve is, for example, as
Molecular sieves or
Molecular sieves, preferably
A molecular sieve; preferably, the mass molar ratio of the molecular sieve to the compound shown in the formula VI is 0.1g to 11g, for example 0.5g;
(3) In the first embodiment, the
Independently is unsubstituted or Ar 1-1 Substituted C 6 ～C 15 Aryl or unsubstituted 5-to 6-membered heteroaryl with one or more heteroatoms selected from N, O and S, and 1 to 3 heteroatoms, preferably unsubstituted or Ar 1-1 Substituted C 6 ～C 15 An aryl group; ar (Ar) 1-1 Is amino, halogen, C 1 ～C 8 Alkyl, halo C 1 ～C 8 Alkyl radical, C 6 ～C 15 Aryl radical, C 1 ～C 8 Alkoxy or C 1 ～C 8 alkyl-O (C = O) -, preferably halogen, C 1 ～C 8 Alkyl or C 6 ～C 15 An aryl group;
(4) In the second embodiment, the
Independently is unsubstituted C 6 ～C 15 Aryl groups such as phenyl;
(5) In the first and second embodiments, in the insertion reaction, the organic solvent is a halogenated hydrocarbon solvent, such as one or more selected from dichloromethane, chloroform, 1, 2-dichloroethane, 1, 2-tetrachloroethane, and carbon tetrachloride, preferably dichloromethane;
(6) In the first scheme, in the insertion reaction, the palladium catalyst is selected from one or more of palladium chloride, palladium acetate, tetratriphenylphosphine palladium, bis (triphenylphosphine) palladium dichloride, 1' -bis (diphenylphosphino) ferrocene ] palladium dichloride, bis (dibenzylideneacetone) palladium, bis (tri-tert-butylphosphino) palladium, bis (tricyclohexylphosphine) palladium dichloride, bis [1, 2-bis (diphenylphosphino) ethane ] palladium, tris (dibenzylideneacetone) dipalladium, palladium pivalate, bis (acetonitrile) palladium dichloride, tetrakis (tri-tert-butylphosphino) palladium and bis (cyanophenyl) palladium dichloride, and is preferably bis (cyanophenyl) palladium dichloride;
(7) In the second scheme, in the insertion reaction, the copper catalyst is selected from one or more of cuprous chloride, cuprous bromide, cuprous iodide, cuprous cyanide, copper tetraacetonitrile hexafluorophosphate, copper tetraacetonitrile tetrafluoroborate, cuprous dimethyl sulfide bromide complex, cuprous hexafluorophosphate, cuprous toluene trifluoromethanesulfonate complex, cuprous benzene trifluoromethanesulfonate complex, cupric chloride, cupric bromide, cupric sulfate, cupric perchlorate, copper bistrifluoromethanesulfonylimide and copper trifluoromethanesulfonate; preferably copper tetra-acetonitrile hexafluorophosphate;
(8) In the first and second embodiments, in the insertion reaction, the complex salt is selected from one or more of sodium tetrakis (3, 5-bis (trifluoromethyl) phenyl) borate, silver hexafluoroantimonate, silver tetrafluoroborate and silver bistrifluoromethanesulfonylimide, preferably sodium tetrakis (3, 5-bis (trifluoromethyl) phenyl) borate;
(9) In the first scheme, in the insertion reaction, the molar ratio of the palladium catalyst to the compound shown in the formula VI is 1;
(10) In the second scheme, in the insertion reaction, the molar ratio of the copper catalyst to the compound shown in the formula VI is 1;
(11) In the first embodiment, in the insertion reaction, the molar ratio of the compound represented by formula I or formula II to the compound represented by formula VI is 1;
(12) In the second scheme, in the insertion reaction, the molar ratio of the compound shown in formula I or formula II to the compound shown in formula VI is 1;
(13) In the first scheme, in the insertion reaction, the molar ratio of the coordination salt to the compound shown in the formula VI is 1;
(14) In the second scheme, in the insertion reaction, the molar ratio of the coordination salt to the compound shown in the formula VI is 1;
(15) In the first embodiment, in the insertion reaction, the molar ratio of the compound represented by the formula VII to the compound represented by the formula VI is 0.5;
(16) In the second scheme, in the insertion reaction, the molar ratio of the compound shown in the formula VIII to the compound shown in the formula VI is 0.5;
(17) In the first and second schemes, in the insertion reaction, the molar concentration of the compound shown in the formula VI in the organic solvent is 0.05-0.5mol/L, such as 0.2mol/L;
(18) In the first scheme, the temperature of the insertion reaction is-10-110 ℃, for example, 20-40 ℃;
(19) In the second embodiment, the temperature of the insertion reaction is-10-70 deg.C, such as 20-40 deg.C.
19. Use according to claim 18, characterized in that it satisfies one or more of the following conditions:
(1) In the first aspect, the
Is composed of
(2) In the first embodiment, the
Is composed of
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