WO2007071345A1 - Sulfonated phosphine ligands and process for cross-coupling aryl halides and arylsulfonates and heteroaryl halides and heteroarylsulfonates with amines, alcohols and carbon nucleophiles by using the ligands in conjunction with transition metal catalysts - Google Patents
Sulfonated phosphine ligands and process for cross-coupling aryl halides and arylsulfonates and heteroaryl halides and heteroarylsulfonates with amines, alcohols and carbon nucleophiles by using the ligands in conjunction with transition metal catalysts Download PDFInfo
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- WO2007071345A1 WO2007071345A1 PCT/EP2006/012107 EP2006012107W WO2007071345A1 WO 2007071345 A1 WO2007071345 A1 WO 2007071345A1 EP 2006012107 W EP2006012107 W EP 2006012107W WO 2007071345 A1 WO2007071345 A1 WO 2007071345A1
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- Prior art keywords
- group
- optionally substituted
- radicals
- aryl
- substituted
- Prior art date
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- 239000003446 ligand Substances 0.000 title claims abstract description 44
- 239000003054 catalyst Substances 0.000 title claims abstract description 31
- 238000006880 cross-coupling reaction Methods 0.000 title claims abstract description 17
- 150000003003 phosphines Chemical class 0.000 title claims abstract description 5
- -1 heteroaryl halides Chemical class 0.000 title claims description 48
- 238000000034 method Methods 0.000 title claims description 29
- 230000008569 process Effects 0.000 title claims description 17
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 title claims description 11
- 229910052799 carbon Inorganic materials 0.000 title claims description 11
- 150000001298 alcohols Chemical class 0.000 title claims description 8
- 239000012038 nucleophile Substances 0.000 title claims description 8
- 229910052723 transition metal Inorganic materials 0.000 title claims description 7
- 150000003624 transition metals Chemical class 0.000 title claims description 7
- 150000001412 amines Chemical class 0.000 title claims description 5
- 150000001502 aryl halides Chemical class 0.000 title description 2
- 125000005228 aryl sulfonate group Chemical group 0.000 title 1
- 125000003118 aryl group Chemical group 0.000 claims description 48
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 30
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 29
- 125000001072 heteroaryl group Chemical group 0.000 claims description 23
- 238000006243 chemical reaction Methods 0.000 claims description 22
- 125000000217 alkyl group Chemical group 0.000 claims description 18
- 239000000203 mixture Substances 0.000 claims description 17
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 16
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 16
- 229910052760 oxygen Inorganic materials 0.000 claims description 16
- 125000001273 sulfonato group Chemical group [O-]S(*)(=O)=O 0.000 claims description 16
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
- 125000004122 cyclic group Chemical group 0.000 claims description 14
- 239000001257 hydrogen Substances 0.000 claims description 14
- 229910052739 hydrogen Inorganic materials 0.000 claims description 14
- 150000001875 compounds Chemical class 0.000 claims description 12
- PXHVJJICTQNCMI-UHFFFAOYSA-N nickel Substances [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 claims description 12
- 229910052757 nitrogen Inorganic materials 0.000 claims description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
- 239000002904 solvent Substances 0.000 claims description 10
- 229910052763 palladium Inorganic materials 0.000 claims description 9
- 229910052717 sulfur Inorganic materials 0.000 claims description 9
- 239000002585 base Substances 0.000 claims description 8
- 229910052759 nickel Inorganic materials 0.000 claims description 8
- 239000000376 reactant Substances 0.000 claims description 8
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 6
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims description 6
- 125000002947 alkylene group Chemical group 0.000 claims description 6
- 239000000460 chlorine Substances 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- 229910052751 metal Inorganic materials 0.000 claims description 6
- 239000002184 metal Substances 0.000 claims description 6
- 229910052698 phosphorus Inorganic materials 0.000 claims description 6
- 239000011574 phosphorus Substances 0.000 claims description 6
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 5
- 125000001931 aliphatic group Chemical group 0.000 claims description 5
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- 125000001769 aryl amino group Chemical group 0.000 claims description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 5
- 229910052794 bromium Inorganic materials 0.000 claims description 5
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 5
- 239000011737 fluorine Substances 0.000 claims description 5
- 229910052731 fluorine Inorganic materials 0.000 claims description 5
- 125000005549 heteroarylene group Chemical group 0.000 claims description 5
- 239000001301 oxygen Substances 0.000 claims description 5
- 125000001424 substituent group Chemical group 0.000 claims description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- 239000003341 Bronsted base Substances 0.000 claims description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 4
- 125000004414 alkyl thio group Chemical group 0.000 claims description 4
- 125000001118 alkylidene group Chemical group 0.000 claims description 4
- 125000005110 aryl thio group Chemical group 0.000 claims description 4
- 125000000732 arylene group Chemical group 0.000 claims description 4
- 229910052742 iron Inorganic materials 0.000 claims description 4
- 150000002829 nitrogen Chemical class 0.000 claims description 4
- 150000003839 salts Chemical class 0.000 claims description 4
- 150000004756 silanes Chemical class 0.000 claims description 4
- 239000011593 sulfur Substances 0.000 claims description 4
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 3
- 239000003513 alkali Substances 0.000 claims description 3
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 3
- 125000003282 alkyl amino group Chemical group 0.000 claims description 3
- 125000004947 alkyl aryl amino group Chemical group 0.000 claims description 3
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 3
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 3
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims description 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
- 125000004986 diarylamino group Chemical group 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 3
- 229910052741 iridium Inorganic materials 0.000 claims description 3
- 229910052748 manganese Inorganic materials 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 150000002902 organometallic compounds Chemical class 0.000 claims description 3
- 229910052697 platinum Inorganic materials 0.000 claims description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
- 229910052703 rhodium Inorganic materials 0.000 claims description 3
- 239000010948 rhodium Substances 0.000 claims description 3
- 239000011877 solvent mixture Substances 0.000 claims description 3
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 3
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 claims description 3
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 2
- 229910019142 PO4 Inorganic materials 0.000 claims description 2
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 claims description 2
- 150000001342 alkaline earth metals Chemical class 0.000 claims description 2
- 150000007942 carboxylates Chemical class 0.000 claims description 2
- 229910052802 copper Inorganic materials 0.000 claims description 2
- 239000010949 copper Substances 0.000 claims description 2
- 150000004292 cyclic ethers Chemical class 0.000 claims description 2
- 125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 claims description 2
- 125000002573 ethenylidene group Chemical group [*]=C=C([H])[H] 0.000 claims description 2
- 150000003949 imides Chemical class 0.000 claims description 2
- 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 claims description 2
- 229920000570 polyether Polymers 0.000 claims description 2
- 239000012041 precatalyst Substances 0.000 claims description 2
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 claims description 2
- 229910000077 silane Inorganic materials 0.000 claims description 2
- 125000005156 substituted alkylene group Chemical group 0.000 claims description 2
- 125000004434 sulfur atom Chemical group 0.000 claims description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims 1
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical group [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 claims 1
- 150000004703 alkoxides Chemical class 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims 1
- 239000010452 phosphate Substances 0.000 claims 1
- VXPLXMJHHKHSOA-UHFFFAOYSA-N propham Chemical compound CC(C)OC(=O)NC1=CC=CC=C1 VXPLXMJHHKHSOA-UHFFFAOYSA-N 0.000 claims 1
- 150000005846 sugar alcohols Polymers 0.000 claims 1
- 150000003512 tertiary amines Chemical class 0.000 claims 1
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 69
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 32
- 230000008878 coupling Effects 0.000 description 25
- 238000010168 coupling process Methods 0.000 description 25
- 238000005859 coupling reaction Methods 0.000 description 25
- 150000003254 radicals Chemical class 0.000 description 25
- 238000006555 catalytic reaction Methods 0.000 description 16
- 150000003871 sulfonates Chemical class 0.000 description 16
- 239000012071 phase Substances 0.000 description 12
- 239000011541 reaction mixture Substances 0.000 description 12
- 238000001816 cooling Methods 0.000 description 11
- YRGAYAGBVIXNAQ-UHFFFAOYSA-N 1-chloro-4-methoxybenzene Chemical compound COC1=CC=C(Cl)C=C1 YRGAYAGBVIXNAQ-UHFFFAOYSA-N 0.000 description 10
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- 150000002825 nitriles Chemical class 0.000 description 10
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- VVAKEQGKZNKUSU-UHFFFAOYSA-N 2,3-dimethylaniline Chemical compound CC1=CC=CC(N)=C1C VVAKEQGKZNKUSU-UHFFFAOYSA-N 0.000 description 8
- UEXCJVNBTNXOEH-UHFFFAOYSA-N Ethynylbenzene Chemical group C#CC1=CC=CC=C1 UEXCJVNBTNXOEH-UHFFFAOYSA-N 0.000 description 8
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 8
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 8
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 8
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 7
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 7
- 239000011777 magnesium Substances 0.000 description 7
- 229910052749 magnesium Inorganic materials 0.000 description 7
- 239000012074 organic phase Substances 0.000 description 7
- 239000011135 tin Substances 0.000 description 7
- 229910052718 tin Inorganic materials 0.000 description 7
- 229920002554 vinyl polymer Polymers 0.000 description 7
- 239000011701 zinc Substances 0.000 description 7
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 6
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 6
- 125000000524 functional group Chemical group 0.000 description 6
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- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 6
- 229910052725 zinc Inorganic materials 0.000 description 6
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 5
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical group [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 5
- 150000001336 alkenes Chemical class 0.000 description 5
- 229910052796 boron Inorganic materials 0.000 description 5
- 229910000029 sodium carbonate Inorganic materials 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- 238000010626 work up procedure Methods 0.000 description 5
- BIWQNIMLAISTBV-UHFFFAOYSA-N (4-methylphenyl)boronic acid Chemical compound CC1=CC=C(B(O)O)C=C1 BIWQNIMLAISTBV-UHFFFAOYSA-N 0.000 description 4
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- NHWQMJMIYICNBP-UHFFFAOYSA-N 2-chlorobenzonitrile Chemical compound ClC1=CC=CC=C1C#N NHWQMJMIYICNBP-UHFFFAOYSA-N 0.000 description 4
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- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
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- QULYNCCPRWKEMF-UHFFFAOYSA-N parachlorobenzotrifluoride Chemical compound FC(F)(F)C1=CC=C(Cl)C=C1 QULYNCCPRWKEMF-UHFFFAOYSA-N 0.000 description 2
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- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
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- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- KNXQDJCZSVHEIW-UHFFFAOYSA-N (3-fluorophenyl)boronic acid Chemical compound OB(O)C1=CC=CC(F)=C1 KNXQDJCZSVHEIW-UHFFFAOYSA-N 0.000 description 1
- PTHGDVCPCZKZKR-UHFFFAOYSA-N (4-chlorophenyl)methanol Chemical compound OCC1=CC=C(Cl)C=C1 PTHGDVCPCZKZKR-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- QCYZMMVPXNWSJK-UHFFFAOYSA-N 1-[4-(2-phenylethynyl)phenyl]ethanone Chemical compound C1=CC(C(=O)C)=CC=C1C#CC1=CC=CC=C1 QCYZMMVPXNWSJK-UHFFFAOYSA-N 0.000 description 1
- LWZYUACNWRVDDJ-UHFFFAOYSA-N 1-benzoxepine Chemical compound O1C=CC=CC2=CC=CC=C12 LWZYUACNWRVDDJ-UHFFFAOYSA-N 0.000 description 1
- QPKFVRWIISEVCW-UHFFFAOYSA-N 1-butane boronic acid Chemical compound CCCCB(O)O QPKFVRWIISEVCW-UHFFFAOYSA-N 0.000 description 1
- BXXYBNVPUWTQFR-UHFFFAOYSA-N 1-methoxy-4-(2-phenylethynyl)benzene Chemical compound C1=CC(OC)=CC=C1C#CC1=CC=CC=C1 BXXYBNVPUWTQFR-UHFFFAOYSA-N 0.000 description 1
- ASKBXZKXIBPNRA-UHFFFAOYSA-N 1-methoxy-4-(4-methylphenyl)benzene Chemical group C1=CC(OC)=CC=C1C1=CC=C(C)C=C1 ASKBXZKXIBPNRA-UHFFFAOYSA-N 0.000 description 1
- RHDYQUZYHZWTCI-UHFFFAOYSA-N 1-methoxy-4-phenylbenzene Chemical group C1=CC(OC)=CC=C1C1=CC=CC=C1 RHDYQUZYHZWTCI-UHFFFAOYSA-N 0.000 description 1
- WJFKNYWRSNBZNX-UHFFFAOYSA-N 10H-phenothiazine Chemical compound C1=CC=C2NC3=CC=CC=C3SC2=C1 WJFKNYWRSNBZNX-UHFFFAOYSA-N 0.000 description 1
- TZMSYXZUNZXBOL-UHFFFAOYSA-N 10H-phenoxazine Chemical compound C1=CC=C2NC3=CC=CC=C3OC2=C1 TZMSYXZUNZXBOL-UHFFFAOYSA-N 0.000 description 1
- NMRRHBBUTOXXPH-UHFFFAOYSA-N 2-(4-chlorophenyl)propanedinitrile Chemical compound ClC1=CC=C(C(C#N)C#N)C=C1 NMRRHBBUTOXXPH-UHFFFAOYSA-N 0.000 description 1
- ZGQVZLSNEBEHFN-UHFFFAOYSA-N 2-(4-methylphenyl)benzonitrile Chemical group C1=CC(C)=CC=C1C1=CC=CC=C1C#N ZGQVZLSNEBEHFN-UHFFFAOYSA-N 0.000 description 1
- LAXBNTIAOJWAOP-UHFFFAOYSA-N 2-chlorobiphenyl Chemical group ClC1=CC=CC=C1C1=CC=CC=C1 LAXBNTIAOJWAOP-UHFFFAOYSA-N 0.000 description 1
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 description 1
- GZWRLASRKFZSQQ-UHFFFAOYSA-N 4-(2-oxocyclohexyl)benzonitrile Chemical compound O=C1CCCCC1C1=CC=C(C#N)C=C1 GZWRLASRKFZSQQ-UHFFFAOYSA-N 0.000 description 1
- ZANPJXNYBVVNSD-UHFFFAOYSA-N 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=C(N)C=C1 ZANPJXNYBVVNSD-UHFFFAOYSA-N 0.000 description 1
- NLPHXWGWBKZSJC-UHFFFAOYSA-N 4-acetylbenzonitrile Chemical compound CC(=O)C1=CC=C(C#N)C=C1 NLPHXWGWBKZSJC-UHFFFAOYSA-N 0.000 description 1
- XDJAAZYHCCRJOK-UHFFFAOYSA-N 4-methoxybenzonitrile Chemical compound COC1=CC=C(C#N)C=C1 XDJAAZYHCCRJOK-UHFFFAOYSA-N 0.000 description 1
- HSGUYVCQKRLJFD-UHFFFAOYSA-N 4-phenacylbenzonitrile Chemical compound C=1C=CC=CC=1C(=O)CC1=CC=C(C#N)C=C1 HSGUYVCQKRLJFD-UHFFFAOYSA-N 0.000 description 1
- IVURTNNWJAPOML-UHFFFAOYSA-N 5,10-dihydrophenazine Chemical compound C1=CC=C2NC3=CC=CC=C3NC2=C1 IVURTNNWJAPOML-UHFFFAOYSA-N 0.000 description 1
- GJCOSYZMQJWQCA-UHFFFAOYSA-N 9H-xanthene Chemical compound C1=CC=C2CC3=CC=CC=C3OC2=C1 GJCOSYZMQJWQCA-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- LGEHVJFCTMEUDU-UHFFFAOYSA-N C1=CC(C=CC(=O)OCCCC)=CC=C1C(=O)C1=CC=CC=C1 Chemical compound C1=CC(C=CC(=O)OCCCC)=CC=C1C(=O)C1=CC=CC=C1 LGEHVJFCTMEUDU-UHFFFAOYSA-N 0.000 description 1
- DRSHXJFUUPIBHX-UHFFFAOYSA-N COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 Chemical compound COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 DRSHXJFUUPIBHX-UHFFFAOYSA-N 0.000 description 1
- 238000005787 Castro-Stephens coupling reaction Methods 0.000 description 1
- PHTOWWPGFXEOCZ-UHFFFAOYSA-N FS(F)(F)(F)F Chemical compound FS(F)(F)(F)F PHTOWWPGFXEOCZ-UHFFFAOYSA-N 0.000 description 1
- 238000007341 Heck reaction Methods 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- HQABUPZFAYXKJW-UHFFFAOYSA-N N-butylamine Natural products CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 1
- 150000001422 N-substituted pyrroles Chemical class 0.000 description 1
- 238000006411 Negishi coupling reaction Methods 0.000 description 1
- 229910021586 Nickel(II) chloride Inorganic materials 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 238000003477 Sonogashira cross-coupling reaction Methods 0.000 description 1
- 238000006619 Stille reaction Methods 0.000 description 1
- 238000006161 Suzuki-Miyaura coupling reaction Methods 0.000 description 1
- ARFYUEZWYRMBSO-VOTSOKGWSA-N [4-[(e)-2-phenylethenyl]phenyl]methanol Chemical compound C1=CC(CO)=CC=C1\C=C\C1=CC=CC=C1 ARFYUEZWYRMBSO-VOTSOKGWSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000001252 acrylic acid derivatives Chemical class 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 229910001854 alkali hydroxide Inorganic materials 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 125000005025 alkynylaryl group Chemical group 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000001448 anilines Chemical class 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Natural products C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 description 1
- 150000001454 anthracenes Chemical class 0.000 description 1
- 229940111121 antirheumatic drug quinolines Drugs 0.000 description 1
- 150000001491 aromatic compounds Chemical class 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 150000004792 aryl magnesium halides Chemical class 0.000 description 1
- 125000004104 aryloxy group Chemical group 0.000 description 1
- 150000001555 benzenes Chemical class 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- 229940077388 benzenesulfonate Drugs 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- UYANAUSDHIFLFQ-UHFFFAOYSA-N borinic acid Chemical class OB UYANAUSDHIFLFQ-UHFFFAOYSA-N 0.000 description 1
- 150000001638 boron Chemical class 0.000 description 1
- 150000001642 boronic acid derivatives Chemical class 0.000 description 1
- 125000005620 boronic acid group Chemical class 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229910052792 caesium Inorganic materials 0.000 description 1
- TVFDJXOCXUVLDH-UHFFFAOYSA-N caesium atom Chemical compound [Cs] TVFDJXOCXUVLDH-UHFFFAOYSA-N 0.000 description 1
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
- 229910000024 caesium carbonate Inorganic materials 0.000 description 1
- 150000001733 carboxylic acid esters Chemical class 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 230000009918 complex formation Effects 0.000 description 1
- 150000001907 coumarones Chemical class 0.000 description 1
- 239000007819 coupling partner Substances 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 238000010502 deborylation reaction Methods 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 125000005266 diarylamine group Chemical group 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000012834 electrophilic reactant Substances 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 125000005610 enamide group Chemical group 0.000 description 1
- 150000002081 enamines Chemical class 0.000 description 1
- YFXCNIVBAVFOBX-UHFFFAOYSA-N ethenylboronic acid Chemical compound OB(O)C=C YFXCNIVBAVFOBX-UHFFFAOYSA-N 0.000 description 1
- 125000005677 ethinylene group Chemical group [*:2]C#C[*:1] 0.000 description 1
- IIEWJVIFRVWJOD-UHFFFAOYSA-N ethyl cyclohexane Natural products CCC1CCCCC1 IIEWJVIFRVWJOD-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction 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
- 239000012847 fine chemical Substances 0.000 description 1
- 150000002222 fluorine compounds Chemical class 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 150000002390 heteroarenes Chemical class 0.000 description 1
- 125000005223 heteroarylcarbonyl group Chemical group 0.000 description 1
- 125000005368 heteroarylthio group Chemical group 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 238000009815 homocoupling reaction Methods 0.000 description 1
- 150000007857 hydrazones Chemical class 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 150000004679 hydroxides Chemical class 0.000 description 1
- 150000002475 indoles Chemical class 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 239000002608 ionic liquid Substances 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- QDLAGTHXVHQKRE-UHFFFAOYSA-N lichenxanthone Natural products COC1=CC(O)=C2C(=O)C3=C(C)C=C(OC)C=C3OC2=C1 QDLAGTHXVHQKRE-UHFFFAOYSA-N 0.000 description 1
- LZWQNOHZMQIFBX-UHFFFAOYSA-N lithium;2-methylpropan-2-olate Chemical compound [Li+].CC(C)(C)[O-] LZWQNOHZMQIFBX-UHFFFAOYSA-N 0.000 description 1
- IWCVDCOJSPWGRW-UHFFFAOYSA-M magnesium;benzene;chloride Chemical compound [Mg+2].[Cl-].C1=CC=[C-]C=C1 IWCVDCOJSPWGRW-UHFFFAOYSA-M 0.000 description 1
- CUONGYYJJVDODC-UHFFFAOYSA-N malononitrile Chemical compound N#CCC#N CUONGYYJJVDODC-UHFFFAOYSA-N 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- BIXUVFQDLJQWLI-UHFFFAOYSA-N n-(2,3-dimethylphenyl)naphthalen-1-amine Chemical compound CC1=CC=CC(NC=2C3=CC=CC=C3C=CC=2)=C1C BIXUVFQDLJQWLI-UHFFFAOYSA-N 0.000 description 1
- 150000002790 naphthalenes Chemical class 0.000 description 1
- KPSSIOMAKSHJJG-UHFFFAOYSA-N neopentyl alcohol Chemical compound CC(C)(C)CO KPSSIOMAKSHJJG-UHFFFAOYSA-N 0.000 description 1
- 150000002816 nickel compounds Chemical class 0.000 description 1
- QMMRZOWCJAIUJA-UHFFFAOYSA-L nickel dichloride Chemical compound Cl[Ni]Cl QMMRZOWCJAIUJA-UHFFFAOYSA-L 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 125000001477 organic nitrogen group Chemical group 0.000 description 1
- 150000002901 organomagnesium compounds Chemical class 0.000 description 1
- NFBOHOGPQUYFRF-UHFFFAOYSA-N oxanthrene Chemical compound C1=CC=C2OC3=CC=CC=C3OC2=C1 NFBOHOGPQUYFRF-UHFFFAOYSA-N 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 150000002923 oximes Chemical class 0.000 description 1
- 229940100684 pentylamine Drugs 0.000 description 1
- 229950000688 phenothiazine Drugs 0.000 description 1
- GJSGGHOYGKMUPT-UHFFFAOYSA-N phenoxathiine Chemical compound C1=CC=C2OC3=CC=CC=C3SC2=C1 GJSGGHOYGKMUPT-UHFFFAOYSA-N 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- XYFCBTPGUUZFHI-UHFFFAOYSA-N phosphine group Chemical group P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 239000003880 polar aprotic solvent Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000011698 potassium fluoride Substances 0.000 description 1
- 235000003270 potassium fluoride Nutrition 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 239000003586 protic polar solvent Substances 0.000 description 1
- 150000003216 pyrazines Chemical class 0.000 description 1
- 150000004892 pyridazines Chemical class 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 150000003248 quinolines Chemical class 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- MNWBNISUBARLIT-UHFFFAOYSA-N sodium cyanide Chemical compound [Na+].N#[C-] MNWBNISUBARLIT-UHFFFAOYSA-N 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 150000003440 styrenes Chemical class 0.000 description 1
- 125000005415 substituted alkoxy group Chemical group 0.000 description 1
- 238000006277 sulfonation reaction Methods 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- GVIJJXMXTUZIOD-UHFFFAOYSA-N thianthrene Chemical compound C1=CC=C2SC3=CC=CC=C3SC2=C1 GVIJJXMXTUZIOD-UHFFFAOYSA-N 0.000 description 1
- 125000005323 thioketone group Chemical class 0.000 description 1
- 150000003606 tin compounds Chemical class 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 1
- 238000007832 transition metal-catalyzed coupling reaction Methods 0.000 description 1
- SYUVAXDZVWPKSI-UHFFFAOYSA-N tributyl(phenyl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=CC=CC=C1 SYUVAXDZVWPKSI-UHFFFAOYSA-N 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 150000003752 zinc compounds Chemical class 0.000 description 1
Classifications
-
- 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
- B01J31/24—Phosphines, i.e. phosphorus bonded to only carbon atoms, or to both carbon and hydrogen atoms, including e.g. sp2-hybridised phosphorus compounds such as phosphabenzene, phosphole or anionic phospholide ligands
- B01J31/2404—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring
- B01J31/2442—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring comprising condensed ring systems
- B01J31/2447—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring comprising condensed ring systems and phosphine-P atoms as substituents on a ring of the condensed system or on a further attached ring
- B01J31/2452—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring comprising condensed ring systems and phosphine-P atoms as substituents on a ring of the condensed system or on a further attached ring with more than one complexing phosphine-P atom
- B01J31/2457—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring comprising condensed ring systems and phosphine-P atoms as substituents on a ring of the condensed system or on a further attached ring with more than one complexing phosphine-P atom comprising aliphatic or saturated rings, e.g. Xantphos
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
- C07C209/04—Preparation of compounds containing amino groups bound to a carbon skeleton by substitution of functional groups by amino groups
- C07C209/06—Preparation of compounds containing amino groups bound to a carbon skeleton by substitution of functional groups by amino groups by substitution of halogen atoms
- C07C209/10—Preparation of compounds containing amino groups bound to a carbon skeleton by substitution of functional groups by amino groups by substitution of halogen atoms with formation of amino groups bound to carbon atoms of six-membered aromatic rings or from amines having nitrogen atoms bound to carbon atoms of six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
- C07C209/66—Preparation of compounds containing amino groups bound to a carbon skeleton from or via metallo-organic compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C213/02—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions involving the formation of amino groups from compounds containing hydroxy groups or etherified or esterified hydroxy groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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Definitions
- aryl- or heteroaryl-substituted alkyl / arylamines and also aryl- or heteroaryl-substituted alkyl / aryl ethers, in particular having functional groups in the alkyl chain, are as well as unsymmetrical biaryls and heterobiaryls and also functionalized alkyl, vinyl and alkynylaryls or heteroaryls important and extremely versatile intermediates in organic synthesis. Importance in modern organic synthesis is limited only by limitations on the accessibility of these classes of compounds.
- Standard method for the preparation of mixed aryl- or heteroaryl-substituted alkyl / arylamines and aryl- or heteroaryl-substituted alkyl / aryl ethers is the L /// ma ⁇ n reaction, the reaction requires very high temperatures to run completely. However, these usually harsh reaction conditions rarely tolerate functional groups and reactive heteroaromatics and are not or only very poorly applicable to electron-deficient aromatics and difficult to control. Modern processes for preparing these amines use Pd or Ni catalysis in the presence of various ligands.
- Standard methods for the preparation of mixed asymmetric biaryl and heterobiarylene and alkyl-, vinyl- and alkynylarylene and heteroarylene are transition metal-catalyzed coupling reactions of aryl, heteroaryl or vinyl halides and sulfonates with aromatic or heteroaromatic carbon electrophiles, in particular organoboron compounds (Suzuki-Miyaura coupling ), Organomagnesium compounds (Kumada-Tamao-Corriu coupling), organozinc compounds (Negishi coupling), organostannanes (Stille coupling), and alkenes (Heck reaction) and terminal alkynes (Sonogashira and Stephens-Castro coupling).
- organoboron compounds Sudzuki-Miyaura coupling
- Organomagnesium compounds Kumada-Tamao-Corriu coupling
- organozinc compounds Negishi coupling
- organostannanes Stille coupling
- the present invention solves all of these problems and relates to novel sulfonated phosphine ligands and their use in combination with transition metals for various cross-coupling reactions.
- the ligands of the invention have the following structure:
- the radicals Ri- ⁇ stand for substituents from the group ⁇ hydrogen, methyl, primary, secondary or tertiary, cyclic or acyclic alkyl radicals having 2 to 20 C atoms, in which optionally one or more hydrogen atoms are replaced by fluorine or chlorine or bromine ( eg CF 3 ), substituted cyclic or acyclic alkyl groups, hydroxy, alkoxy, amino, alkylamino, dialkylamino, arylamino, diarylamino, alkylarylamino, pentafluorosulfuryl, phenyl, substituted phenyl, heteroaryl, substituted heteroaryl, thio, alkylthio, arylthio, diarylphosphino, dialkylphosphino, alkylarylphosphino , optionally substituted aminocarbonyl, CO 2 " , alkyl or aryloxycarbonyl, hydroxyalkyl, alkoxyalkyl,
- Yi and Y 2 are each independently identical or different bridging, di- or trivalent structural elements from the group ⁇ oxygen, sulfur, substituted nitrogen or phosphorus, optionally substituted Ci -3 - alkylene, -vinylene, alkylidene or silaalkylene, optionally substituted arylene or Heteroarylene, carboxylate, thiocarboxylate, N-substituted carboxamide or imide, optionally substituted silane, single bond ⁇ , wherein the middle ring may have aliphatic, heteroaliphatic, aromatic or heteroaromatic character;
- Qi- 4 independently represent identical or different radicals from the group ⁇ hydrogen, methyl, linear, branched or cyclic alkyl, optionally substituted, aryl, heteroaryl, optionally substituted ⁇ or Qi and Q 2 or Q 3 and Q 4 together form a ring and represent a bridging structural element from the group ⁇ optionally substituted alkylene, branched alkylene, cyclic alkylene, optionally substituted arylene or heteroarylene ⁇ or independently of one another for one or two polycyclic radicals, such as norbornyl or adamantyl; Qi -4 may carry one or more sulfonic acid or sulfonate groups.
- ligands are mono- or disulfonated diphosphines based on the basic skeletons of anthracene, acridine, 9,10-dihydroacridine, 9,19-dihydroanthracene, xanthene, phenoxathiin, thianthrene, dibenzo-p-dioxin, phenoxazine, phenothiazine, 5,10 Dihydrophenazine, carbazole, dibenzofuran, dibenzothiophene, (10,11-dihydro-) benzoxepine and -azepin, and the heterocyclic analogs derived therefrom.
- Yi is an optionally substituted alkylene group, alkylidene, vinylidene or vinylene group and Y2 is O and in each case one of the radicals R 1 -R 3 and R 4 -R 6 is a sulfonate group.
- R 1 -R 3 and R 4 -R 6 is a sulfonate group.
- either at least one further of the radicals Ri- 3 and R 4-6 is not hydrogen or at most three of the groups Qi -4 stand for phenyl.
- the ligands according to the invention are used in processes for the cross-coupling of aromatic compounds in conjunction with a transition metal catalyst.
- the invention therefore further relates to novel catalyst systems comprising at least one ligand of the following formula
- the metal can be present in any oxidation state. According to the invention, it is used in cross-coupling reactions in relation to the reactant (I) in amounts of 0.001 mol% to 100 mol%, preferably between 0.01 and 10 mol%, particularly preferably between 0.01 and 1 mol%.
- the catalyst can be added in finished form or form in situ, e.g. from a precatalyst by reduction or hydrolysis or from a metal salt and added ligand by complex formation.
- the catalyst system of the invention is, as will be clarified below, for example, for the following cross-coupling reactions used:
- a process for preparing mixed aryl and heteroarylamines and aryl- or heteroaryl-substituted alkyl / aryl ethers (III) by cross-coupling of primary or secondary alkyl or arylamines, alcohols or phenols (II) with aryl or heteroaryl halides or sulfonates (I).
- catalyst system according to the invention high yields can be achieved even with low catalyst loadings (equation 1), which is characterized by the following advantages: • Very high catalyst activity, as the ligand is an anion in the reaction mixture and has special electronic effects.
- reaction can also be carried out in protic solvents, e.g. substituted alcohols are carried out.
- the structure of the ligand is variable depending on the chosen body and can be adapted to different needs. • Depending on the ligand selected, the bite angle and spacing of the two phosphine groups can be varied to optimize the efficiency of the catalyst.
- Hal is chlorine, bromine or iodine or sulfonates such as trifluoromethanesulfonate (triflate), Nonafluortrimethylmethansulfonat (nonaflate), methanesulfonate, benzenesulfonate, para-toluenesulfonate or methoxy.
- Xi -5 independently represent carbon or the group Xjr 1 is nitrogen, or in each case two adjacent via a formal double bond together are connected XiRj O (furans), S (thiophenes), NH or NRj (pyrroles).
- Preferred compounds of the formula (I) which can be reacted with the catalyst system according to the invention by this process are, for example, benzenes, pyridines, pyrimidines, pyrazines, pyridazines, furans, thiophenes, pyrroles, N-substituted pyrroles or naphthalenes, quinolines, indoles, Benzofurans etc.
- the radicals Ri -5 in Equation 1 are substituents from the group ⁇ hydrogen, methyl, primary, secondary or tertiary, cyclic or acyclic alkyl radicals having 2 to 20 C atoms, in which optionally one or more hydrogen atoms by fluorine or chlorine or bromine substituted, for example CF 3 , substituted cyclic or acyclic alkyl groups, hydroxy, alkoxy, amino, alkylamino, dialkylamino, arylamino, diarylamino, alkylarylamino, pentafluorosulfurane, phenyl, substituted phenyl, heteroaryl, substituted heteroaryl, thio, alkylthio, arylthio, diarylphosphino, dialkylphosphino , Alkylarylphosphino, optionally substituted aminocarbonyl, CO 2 " , alkyl or aryloxycarbonyl, hydroxyalkyl, alkoxyalkyl
- R ' may be the same or different radicals from the group ⁇ hydrogen, methyl, linear, branched C 1 -C 20 alkyl or cyclic alkyl, substituted or unsubstituted phenyl ⁇ .
- R 'and R" independently of one another may stand for identical or different radicals from the group ⁇ hydrogen, methyl, linear, branched C 1 -C 20 alkyl or cyclic alkyl, substituted or unsubstituted phenyl ⁇ or together form a ring and from the group ⁇ optionally substituted alkylene, branched alkylene, cyclic alkylene, substituted azaalkylene, substituted oxaalkylene, substituted phosphaalkylene or optionally substituted sulfaalkylene ⁇ .
- Typical examples of the compound II in Equation 1 are thus methyl, ethyl, 1-methylethyl, propyl, 1-methylpropyl, 2-methylpropyl, 1, 1-dimethylethyl, butyl and pentylamine, cyclopropyl, Cyclobutyl, cyclopentyl, cyclohexylamine, phenyl, benzylamine.
- the catalyst systems of the invention can be used in processes for the formation of C-C bonds by reacting aryl or heteroaryl halides and sulfonates (I) with organic compounds of boron, magnesium, zinc and tin and of silicon (IV).
- aryl or heteroaryl halides and sulfonates I
- organic compounds of boron, magnesium, zinc and tin and of silicon IV
- Organoboron compounds the addition of a Bronsted base in a solvent or solvent mixture makes sense.
- high yields can be achieved by using the catalyst systems of the invention with low catalyst loadings (Equation 2).
- this method additionally offers the possibility of working in aqueous solvent systems.
- Hal and X 1 -X 5, and R1-R5 are as described under A).
- M is boron, magnesium, zinc, silicon or tin.
- R ' may each represent one of a total of n identical or different radicals from the group ⁇ methyl, linear, branched or cyclic substituted or unsubstituted C 1 -C 20 -alkyl, vinyl or alkynyl, substituted or unsubstituted aryl or heteroaryl ⁇ .
- R "can, for M boron, in each case one of a total of m identical or different radicals from the group ⁇ methyl, linear, branched C 1 -C 20 -alkyl or cyclic substituted or unsubstituted alkyl, vinyl or alkinyl, hydroxy, linear, branched or cyclic substituted or unsubstituted C r C 2 o-alkoxy and dialkylamino ⁇ , wherein two or more of these R "may be linked together and form one or more rings;
- R can stand for an O-linked radical R '(Boronklaanhydride).
- R "may for M tin for each are a total of m identical or different radicals from the group ⁇ methyl, linear, branched C 1 -C 2O -alkyl or cyclic substituted or unsubstituted alkyl, vinyl or alkinyl ⁇ .
- Typical examples of compound (IV) are thus aryl or heteroaryl boronic acids and borinic acids (eg 3-fluorophenylboronic acid) and their esters (eg 4-aminophenylboronic acid pinacol ester), tetraarylboranates, vinylboronic acid, butylboronic acid, arylmagnesium halides (eg phenylmagnesium chloride), diarylmagnesium compounds and triarylmagnesates analogous alkyl and aryl zinc compounds, vinyl, alkynyl and aryl trialkyl stannanes and silanes and siloxanes.
- aryl or heteroaryl boronic acids and borinic acids eg 3-fluorophenylboronic acid
- esters eg 4-aminophenylboronic acid pinacol ester
- tetraarylboranates vinylboronic acid, butylboronic acid
- arylmagnesium halides eg phen
- the catalyst system according to the invention for the formation of C-C bonds by reaction of aryl or heteroaryl halides and sulfonates (I) with alkenes (VI) can be used (equation 3).
- process B it is also advantageously possible to work in aqueous solvent systems in this process as well.
- Hal and X 1 -X 5 and RrR 5 may have the meanings described under A).
- R ', R “and R 1 " may be independently hydrogen or any organic and elemental organic substituents, ie, substituents attached via heteroatoms, eg, R 1 O-, R'S-, R'COO-, etc., wherein two or more of these radicals may be linked together and form one or more rings.
- Typical examples of the compound (VI) are thus acrylates, open-chain and cyclic alkenes, styrenes, as well as enamines or enamides.
- the catalyst systems of the invention can be used in cross-coupling processes for the formation of C-C bonds by reacting aryl or heteroaryl halides and sulfonates (I) with terminal alkynes (VIII) (Equation 4). Again, the above advantages are achieved again.
- Hal and X 1 -X 5 and also R 1 -R 5 have the meanings described under a).
- R ' may be hydrogen or any organic and organoelement substituents.
- Typical examples of the compound (VIII) are thus acetylene, aliphatic alkynes, arylalkynes and alkynyl ethers.
- Hal and X 1 -X 5 and R 1 -R 5 have the meanings described under A).
- Equation 5a represents O, S, NR ''',NOR''(protected oxime), NNR 111 R''' (double protected hydrazone) (Equation 5a) or with W together for N alone (Equation 5b).
- R ', R may represent identical or different radicals from the group ⁇ hydrogen, methyl, linear, branched C 1 -C 20 -alkyl or cyclic, optionally substituted alkyl, substituted or unsubstituted aryl or heteroaryl or one not on Reaction participating functional group, for example carbonyl, carboxyl, N-substituted imine or nitrile ⁇ or together form a ring
- W is a radical from the group ⁇ hydrogen, methyl, linear, branched C 1 -C 20 -alkyl or cyclic, optionally substituted alkyl, substituted or unsubstituted aryl or heteroaryl, optionally substituted alkoxy, aryloxy, heteraryloxy, optionally substituted alkylthio, Arylthio, heteroarylthio, optionally substituted dialkylamino, di (hetero) arylamino,
- Alkyl (hetero) arylamino ⁇ and can form a ring with R 1 , R “, R” 1 or R “" (equation 5a).
- Z and W together may represent a nitrile nitrogen (Equation 5b).
- Typical examples of the compounds (Xa) and (Xb) in equations 5 a + b are thus enolizable ketones, aldehydes, N-substituted imines, thioketones, carboxylic esters, thiocarboxylic esters and nitriles.
- the catalyst systems of the invention can be used in processes for the preparation of aryl or heteroaryl nitriles (XIII) by cross-coupling of cyanides (XII) with substituted aryl or heteroaryl compounds (I) (Equation 6), which is also characterized by the advantages mentioned above are distinguished.
- Hal and X1-X5 and R1-R5 have the meanings described under A).
- MCN stands for NaCN, KCN, Zn (CN) 2 , K 3 [Fe (CN) 6 ], K 4 [Fe (CN) 6 ], HCN or a cyanohydrin.
- Bronsted bases to the reaction mixture is necessary in all the processes A) to F) described above-except in case B) when using magnesium, zinc and tin compounds-in order to achieve acceptable reaction rates.
- Suitable bases are hydroxides, carbonates and fluorides of the alkali and alkaline earth metals, carbonates, bicarbonates, amides and phosphates of the alkali metals and their mixtures, and aliphatic amines and other organic nitrogen bases such as pyridines and DBU.
- Particularly suitable for the applications described under A) and E) are the bases of the group ⁇ potassium tert-butoxide, sodium tert-butoxide, cesium tert-butylate, lithium tert-butylate ⁇ ; Particularly suitable for the other applications are the bases of the group ⁇ triethylamine, sodium carbonate, potassium carbonate, cesium carbonate, potassium phosphate, cesium fluoride, potassium fluoride, barium hydroxide ⁇ .
- usually at least the amount of base is used which corresponds to the molar amount of the nucleophile to be coupled, usually 1.0 to 6 equivalents, preferably 1.2 to 3 equivalents of base based on the nucleophile to be coupled used.
- All reactions A) to F) described above are carried out in a suitable solvent or a single- or multi-phase solvent mixture which has sufficient dissolving power for all the reactants involved.
- a suitable solvent or a single- or multi-phase solvent mixture which has sufficient dissolving power for all the reactants involved.
- Well-suited are open-chain and cyclic ethers and diethers, oligo- and polyethers as well as substituted single or multiple alcohols and optionally substituted ones Aromatics, as well as polar aprotic solvents.
- water is also a preferred solvent.
- the reaction can be carried out at temperatures between -30 0 C and the boiling point of the solvent used at the pressure used.
- the implementation at elevated temperatures in the range of -20 to 240 0 C is preferred.
- the concentration of the reactants can be varied within wide limits. Conveniently, the reaction is carried out in the highest possible concentration, wherein the solubilities of the reactants and reagents must be observed in the particular reaction medium. The reaction is preferably carried out in the range from 0.05 to 5 mol / l, based on the reactant present in the deficit.
- Nucleophilic reactants (II), (IV), (VI), (VII) or (X) and electrophilic reactants (I) can be used in molar ratios of 10: 1 to 1:10, preferably ratios of 3: 1 to 1: 3 and particularly preferred are ratios of 1.2: 1 to 1: 1.2.
- all materials are initially charged and the mixture is heated with stirring to the reaction temperature.
- the nucleophile and, if appropriate, further reactants are metered into the reaction mixture during the reaction.
- the workup is usually carried out with a mixture of aromatic hydrocarbons and water with removal of the aqueous phase, which absorbs the inorganic constituents and ligand and transition metal, the product remaining in the organic phase, if non-existent acidic functional groups lead to a different phase behavior.
- ionic liquids can be used to separate the more polar constituents.
- the product is preferably isolated by precipitation or distillation from the organic phase, for example by concentration or by addition of precipitants. Frequently, additional purification, for example by recrystallization or chromatography, is unnecessary.
- the isolated yields are usually in the range of 70 to 100%, preferably in the range> 75% to 100%, in particular> 80% to 100%.
- the inventive method opens up a very economical method, especially in the aqueous workup to
- a) produce mixed aryl and heteroarylamines and aryl or heteroaryl-substituted alkyl / aryl ethers starting from the corresponding primary or secondary alkyl or arylamines, alcohols or phenols or their derivatives and the corresponding aryl or heteroaryl halides or sulfonates; b) unsymmetrical biaryls, heterobiaryls and analogous coupling products starting from the corresponding aryl or heteroaryl halides and sulfonates, in particular the unreactive chlorides, and the corresponding boron derivatives, in particular boronic acids, magnesium, zinc and tin organyls; c) preparing aryl and heteroaryl vinyl compounds starting from the corresponding aryl or heteroaryl halides or sulfonates and the corresponding alkenes; d) aryl and heteroaryl alkynes starting from the corresponding aryl or heteroaryl halides or sulfonates and the
- alkynes To prepare alkynes; e) arylated or heteroarylated carbonyl compounds in the 2-position, their Derivatives and analogues and nitriles starting from the corresponding carbonyl compounds or their derivatives and nitriles and the corresponding aryl or heteroaryl halides or sulfonates; and f) aryl and heteroaryl nitriles starting from the corresponding aryl or heteroaryl halides and sulfonates.
- the bite angle can be modified to achieve the optimal effectiveness of the ligand for the desired application.
- This ligand was prepared according to a protocol of van Leeuwen et al., Adv. Synth. Catal. 2002, 293.
- Example 2 Coupling of chlorobenzene with 2,3-dimethylaniline to N- (2,3-dimethylphenyl) -aniline under L1-Pd catalysis
- Example 3 Coupling of chlorobenzene with 2,3-dimethylaniline to N- (2,3-dimethylphenyl) -aniline under Xantphos-Pd catalysis
- Example 10 Same as Example 10, instead of L1, the commercially available ligand xantphos (4,5-bis-diphenylphosphino-9,9-dimethyl-9H-xanthene), which corresponds to the unsulfonated L1, was used for comparison.
- the product was purified by flash chromatography (eluent cyclohexane / ethyl acetate 10: 1). Only 162 mg (0.82 mmol, 82%) of the product were obtained.
- Example 4 Coupling of 4-chloroanisole with 2,3-dimethylaniline to (2,3-dimethylphenyl) - (4-methoxyphenyl) amine under L1-Pd catalysis
- Example 5 Coupling of 2-bromo-4-fluorotoluene with 2,3-dimethylaniline to 5-fluoro-2,2 ', 3'-trimethyl-diphenylamine under L1-Pd catalysis
- Example 6 Coupling of 1-bromonaphthalene with 2,3-dimethylaniline to (2,3-dimethylphenyl) -naphthalen-1-ylamine under L1-Pd catalysis
- Example 7 Coupling of 4-chloroanisole with 4-tolylboronic acid to 4-methoxy-4'-methylbiphenyl under L1-Pd catalysis
- Example 8 Coupling of 2-chlorobenzonitrile with 4-tolylboronic acid to 2-cyano-4'-methylbiphenyl under L1-Pd catalysis
- Example 12 Coupling of 4-chlorobenzophenone with butyl acrylate to 3- (4-benzoyl-phenyl) -acrylic acid butyl ester under L1-Pd catalysis
- Example 13 Coupling of 4-chlorobenzyl alcohol with styrene to 4-hydroxymethylstilbene under L1-Pd catalysis
- Example 14 Coupling of 4-chloroacetophenone with phenylacetylene to 1- (4-phenylethynylphenyl) -ethanone catalyzed by LI-Pd
- Example 16 Coupling of 4-bromobenzonitrile with acetophenone to 4- (2-oxo-2-phenylethyl) benzonitrile under L1-Pd catalysis
- Example 19 Coupling of 4-chloroacetophenone with zinc cyanide to 4-cyanoacetophenone under L1-Pd catalysis
- Example 20 Coupling of 4-chloroanisole with zinc cyanide to 4-methoxybenzonitrile under L1-Pd catalysis
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Abstract
The invention relates to sulfonated phosphine ligands of the structure and to catalyst systems comprising these ligands and to their use in cross-coupling reactions, where R1-6, X1-10, Y1, Y2, P and Q1-4 are each defined as specified.
Description
Beschreibungdescription
Sulfonierte Phosphanliganden und Verfahren zur Kreuzkupplung von Aryl- undSulfonated phosphine ligands and methods for cross-coupling of aryl and
Heteroarylhalogeniden und -sulfonaten mit Aminen, Alkoholen und Kohlenstoffnucleophilen durch Einsatz der Liganden in Verbindung mit Übergangsmetall-KatalysatorenHeteroaryl halides and sulfonates with amines, alcohols, and carbon nucleophiles through the use of ligands in combination with transition-metal catalysts
Gemischte aryl- bzw. heteroarylsubstituierte Alkyl-/Arylamine sowie aryl- bzw. heteroarylsubstituierte Alkyl-/Arylether, vor allem mit funktionellen Gruppen in der Alkylkette, sind ebenso wie unsymmetrische Biaryle und Heterobiaryle sowie funktionalisierte Alkyl-, Vinyl- und Alkinylaryle bzw. -heteroaryle bedeutsame und äußerst vielseitig verwendbare Zwischenprodukte in der organischen Synthese. Die Bedeutung in der modernen organischen Synthese wird nur durch Limitierungen der Zugänglichkeit dieser Verbindungsklassen eingeschränkt. Standardverfahren zur Herstellung von gemischten aryl- bzw. heteroarylsubstituierte Alkyl-/Arylaminen sowie aryl- bzw. heteroarylsubstituierten Alkyl-/Arylethern ist die L///maπn-Reaktion, wobei die Reaktion sehr hohe Temperaturen benötigt, um vollständig abzulaufen. Jedoch tolerieren diese in der Regel drastischen Reaktionsbedingungen selten funktionelle Gruppen und reaktive Heteroaromaten und sind nicht oder nur sehr schlecht anwendbar auf elektronenarme Aromaten und nur schwierig zu kontrollieren. Moderne Verfahren zur Herstellung dieser Amine bedienen sich der Pd- bzw. Ni-Katalyse in Gegenwart verschiedener Liganden. Standardverfahren zur Herstellung von gemischten asymmetrischen Biarylen und Heterobiarylen sowie Alkyl-, Vinyl- und Alkinylarylen und -heteroarylen sind übergangsmetallkatalysierte Kupplungsreaktionen von Aryl-, Heteroaryl- bzw. Vinylhalogeniden und -sulfonaten mit aromatischen bzw. heteroaromatischen Kohlenstoffelektrophilen, insbesondere Organoborverbindungen (Suzuki-Miyaura- Kupplung), Organomagnesiumverbindungen (Kumada-Tamao-Corriu-Kupplung), Organozinkverbindungen (Negishi-Kupplung), Organostannanen (Stille-Kupplung) sowie Alkenen (Heck-Reaktion) und terminalen Alkinen (Sonogashira- und Stephens- Castro-Kupplung). Eine neuere Entwicklung beinhaltet den Einsatz von Enolaten, die gegebenenfalls in situ gebildet werden können, als Elektrophile. Als Katalysatoren finden hauptsächlich Palladium- und Nickelverbindungen in Kombination mit unterschiedlichen Liganden Verwendung. Die verfügbaren Liganden zeigen jedoch
unterschiedliche Nachteile, insbesondere wenn die wirtschaftlich vorteilhaften Aryl- bzw. Heteroarylchloride als Kupplungspartner zum Einsatz kommen sollen (s.u.).Mixed aryl- or heteroaryl-substituted alkyl / arylamines and also aryl- or heteroaryl-substituted alkyl / aryl ethers, in particular having functional groups in the alkyl chain, are as well as unsymmetrical biaryls and heterobiaryls and also functionalized alkyl, vinyl and alkynylaryls or heteroaryls important and extremely versatile intermediates in organic synthesis. Importance in modern organic synthesis is limited only by limitations on the accessibility of these classes of compounds. Standard method for the preparation of mixed aryl- or heteroaryl-substituted alkyl / arylamines and aryl- or heteroaryl-substituted alkyl / aryl ethers is the L /// maπn reaction, the reaction requires very high temperatures to run completely. However, these usually harsh reaction conditions rarely tolerate functional groups and reactive heteroaromatics and are not or only very poorly applicable to electron-deficient aromatics and difficult to control. Modern processes for preparing these amines use Pd or Ni catalysis in the presence of various ligands. Standard methods for the preparation of mixed asymmetric biaryl and heterobiarylene and alkyl-, vinyl- and alkynylarylene and heteroarylene are transition metal-catalyzed coupling reactions of aryl, heteroaryl or vinyl halides and sulfonates with aromatic or heteroaromatic carbon electrophiles, in particular organoboron compounds (Suzuki-Miyaura coupling ), Organomagnesium compounds (Kumada-Tamao-Corriu coupling), organozinc compounds (Negishi coupling), organostannanes (Stille coupling), and alkenes (Heck reaction) and terminal alkynes (Sonogashira and Stephens-Castro coupling). A recent development involves the use of enolates, which may be formed in situ, as electrophiles. The catalysts used are mainly palladium and nickel compounds in combination with different ligands use. The available ligands, however, show different disadvantages, especially when the economically advantageous aryl or heteroaryl chlorides are to be used as coupling partners (see below).
Es wäre daher sehr wünschenswert, ein Verfahren zu haben, das die Kreuzkupplung von aromatischen und heteroaromatischen Halogeniden und Sulfonaten, insbesondere auch der unreaktiven Chloride, mit Stickstoff-, Sauerstoff- und Kohlenstoffnucleophilen bewerkstelligt, dabei gleichzeitig sehr hohe Ausbeuten erzielt, mit geringen Katalysator- und Ligandmengen auskommt und zusätzlich in wirtschaftlich nutzbaren Verfahren einsetzbar ist, die sich besonders durch einfache Abtrennung von Ligand und Katalysator vom Produkt auszeichnen. Die bisher veröffentlichten Syntheseverfahren lösen dieses Problem nicht bzw. nur teilweise und zeigen viele Nachteile, wie anhand von einigen Beispielen demonstriert werden soll:It would therefore be highly desirable to have a process that accomplishes the cross-coupling of aromatic and heteroaromatic halides and sulfonates, especially the unreactive chlorides, with nitrogen, oxygen and carbon nucleophiles, while achieving very high yields, with low catalyst and Ligand amounts requires and in addition can be used in economically useful process, which are characterized by simple separation of ligand and catalyst from the product. The previously published synthesis methods do not solve this problem or only partially and show many disadvantages, as will be demonstrated by some examples:
• Verwendung teuerer und schwer handhabbarer (teilweise pyrophorer) Liganden z.B. P1Bu3 (zur C-N-Kupplung siehe Hartwig et al., US6100398, zur C-C-Use of expensive and difficult-to-handle (partially pyrophoric) ligands, for example P 1 Bu 3 (for CN coupling see Hartwig et al., US 6100398, to the CC-
Kupplung Fu et al., J. Am. Chem. Soc. 2000, 122, 4020, zur C-C-Kupplung von Enolaten siehe Hartwig et al., US6072073), sowie aufwendige Isolierung des Produktes durch Chromatographie.Coupling Fu et al., J. Am. Chem. Soc. 2000, 122, 4020, for C-C coupling of enolates see Hartwig et al., US6072073), as well as complex isolation of the product by chromatography.
• Verwendung von Liganden, die schwierig zu synthetisieren sind (ferrocenbasierte Liganden, Hartwig et al., WO0211883 und US6057456), aufwendige Isolierung des Produktes durch ChromatographieUse of ligands which are difficult to synthesize (ferrocene-based ligands, Hartwig et al., WO0211883 and US6057456), extensive isolation of the product by chromatography
• aufwendige bzw. schwierige Ligandensynthesen (Buchwald et al.,• elaborate or difficult ligand syntheses (Buchwald et al.,
WO 00/02887), aufwendige Isolierung des Produktes durch ChromatographieWO 00/02887), extensive isolation of the product by chromatography
• schwierige Abtrennbarkeit von Ligand- und Katalysatorresten erfordern häufig separate Reinigungsschritte, teilweise unter Zuhilfenahme teurer• difficult separability of ligand and catalyst residues often require separate purification steps, sometimes with the help of expensive
Spezialreagentien (Garrett, Prasad, Adv. Synth. Catal. 2004, 346, 889), da insbesondere für Pharma-Feinchemikalien sehr niedrige Spezifikationsgrenzen einzuhalten sind (z. B. < 10 oder < 5 ppm). Zusätzlich sind die üblicherweise verwendeten Katalysatorsysteme in verschiedenen anderen Reaktionen hochaktiv, so dass auch in Folgestufen unerwünschte Nebenreaktionen katalysiert werden können.Special reagents (Garrett, Prasad, Adv. Synth.Catal., 2004, 346, 889), since, in particular for pharmaceutical fine chemicals, very low specification limits must be maintained (eg <10 or <5 ppm). In addition, the catalyst systems commonly used are highly active in various other reactions, so that even in subsequent stages unwanted side reactions can be catalyzed.
Weitere Arbeiten zur Synthese der C-N-Bindung aus Arylhalogeniden bzw. -sulfonaten unter Verwendung verschiedener Katalysatoren zeichnen sich durch folgende Nachteile
aus (Wolfe, J. P.; Buchwald, S. L. J. Org. Chem. 2000, 65, 1444; , Wolfe, J. P.; Buchwald, S. L. J. Org. Chem. 2000, 65, 1158; Huang, J.; Grassa, G.; Nolan, S.P. Org. Lett. 1999, 1, 1307; Hartwig, J. F.; Kawatsura, M.; Hauck, S. I.; Shaughnessy, K. H.; Alcazar-Roman, L. M. J. Org. Chem. 1999, 64, 5575; Stauffer, S. I.; Hauck, S. I.; Lee, S.; Stambuli, J.; Hartwig, J. F. Org. Lett. 2000, 2, 1423):Further work for the synthesis of the C-N bond from aryl halides or sulfonates using various catalysts is characterized by the following disadvantages Wolfe, JP; Buchwald, SLJ Org. Chem. 2000, 65, 1444 ;, Wolfe, JP; Buchwald, SLJ Org. Chem. 2000, 65, 1158; Huang, J .; Grassa, G., Nolan, SP Lett., 1999, 1, 1307; Hartwig, JF; Kawatsura, M., Hauck, SI; Shaughnessy, KH; Alcazar-Roman, LMJ Org. Chem. 1999, 64, 5575; Stauffer, SI; Hauck, SI; Lee, S., Stambuli, J .; Hartwig, JF Org. Lett. 2000, 2, 1423):
• Die Temperaturen sind in vielen Fällen sehr hoch• The temperatures are very high in many cases
• Die Selektivitäten für die Bildung der gewünschten Aniline im Gegensatz zu den ungewünschten Arinen bzw. Diarylaminen sind oft niedriger als nötig für ein optimales synthetisches Potential.• The selectivities for the formation of the desired anilines in contrast to the unwanted arynes or diarylamines are often lower than necessary for optimum synthetic potential.
Weitere Verfahren zur Synthese der C-C-Bindung aus Aryl- bzw. Heteroarylhalogeniden und -sulfonaten zeichnen sich durch folgende Nachteile aus:Further processes for the synthesis of the C-C bond from aryl or heteroaryl halides and sulfonates are distinguished by the following disadvantages:
- geringe Aktivität bei der Umsetzung von Aryl- bzw. Heteroarylchloriden, insbesondere, wenn diese elektronenreich sind;low activity in the reaction of aryl or heteroaryl chlorides, especially if they are electron-rich;
- hohe Reaktionstemperaturen sind notwendig;- high reaction temperatures are necessary;
- Nebenreaktionen wie z.B. Homokupplung und Deborylierung treten häufig auf.- side reactions such as Homocoupling and deborylation are common.
Die vorliegende Erfindung löst alle diese Probleme und betrifft neue sulfonierte Phosphanliganden und deren Verwendung in Kombination mit Übergangsmetallen für verschiedene Kreuzkupplungsreaktionen.The present invention solves all of these problems and relates to novel sulfonated phosphine ligands and their use in combination with transition metals for various cross-coupling reactions.
Die erfindungsgemäßen Liganden haben die folgende Struktur:The ligands of the invention have the following structure:
und werden bei Kreuzkupplungsverfahren in Verbindung mit Übergangsmetallen, insbesondere mit Palladium oder Nickel als Katalysator, eingesetzt. Hierbei steht
X4-7 für Kohlenstoff, Stickstoff oder Phosphor, Xi-3 und Xβ-io unabhängig voneinander entweder für Kohlenstoff, oder die Gruppe X1Rj mit i= 2, 3, 4 oder 5 für Stickstoff oder Phosphor oder jeweils zwei benachbarte über eine formale Doppelbindung verbundene XjRi stehen gemeinsam für O (Furane), S (Thiophene), NH oder NRj (Pyrrole);and are used in cross-coupling processes in connection with transition metals, in particular with palladium or nickel as catalyst. This is X 4-7 for carbon, nitrogen or phosphorus, Xi -3 and Xβ-io independently of one another for carbon, or the group X 1 Rj with i = 2, 3, 4 or 5 for nitrogen or phosphorus or two adjacent ones over one formal double bond linked XjRi together represent O (furans), S (thiophenes), NH or NRj (pyrroles);
die Reste Ri-β stehen für Substituenten aus der Gruppe {Wasserstoff, Methyl, primäre, sekundäre oder tertiäre, cyclische oder acyclische Alkylreste mit 2 bis 20 C-Atomen, bei denen gegebenenfalls ein oder mehrere Wasserstoffatome durch Fluor oder Chlor oder Brom ersetzt sind (z.B. CF3), substituierte cyclische oder acyclische Alkylgruppen, Hydroxy, Alkoxy, Amino, Alkylamino, Dialkylamino, Arylamino, Diarylamino, Alkylarylamino, Pentafluorsulfuranyl, Phenyl, substituiertes Phenyl, Heteroaryl, substituiertes Heteroaryl, Thio, Alkylthio, Arylthio, Diarylphosphino, Dialkylphosphino, Alkylarylphosphino, gegebenenfalls substituiertes Aminocarbonyl, CO2 ", Alkyl- oder Aryloxycarbonyl, Hydroxyalkyl, Alkoxyalkyl, Nitro, Cyano, Aryl- oder Alkylsulfon, Aryl- oder Alkylsulfonyl}, oder jeweils zwei benachbarte Reste Ri-5 stehen zusammen für einem aromatischen, heteroaromatischen oder aliphatischen ankondensierten Ring, mit der Maßgabe, dass mindestens einer der Reste Ri-3 und R4-6 einer Sulfonatgruppe entspricht.the radicals Ri-β stand for substituents from the group {hydrogen, methyl, primary, secondary or tertiary, cyclic or acyclic alkyl radicals having 2 to 20 C atoms, in which optionally one or more hydrogen atoms are replaced by fluorine or chlorine or bromine ( eg CF 3 ), substituted cyclic or acyclic alkyl groups, hydroxy, alkoxy, amino, alkylamino, dialkylamino, arylamino, diarylamino, alkylarylamino, pentafluorosulfuryl, phenyl, substituted phenyl, heteroaryl, substituted heteroaryl, thio, alkylthio, arylthio, diarylphosphino, dialkylphosphino, alkylarylphosphino , optionally substituted aminocarbonyl, CO 2 " , alkyl or aryloxycarbonyl, hydroxyalkyl, alkoxyalkyl, nitro, cyano, aryl or alkylsulfone, aryl or alkylsulfonyl}, or in each case two adjacent radicals Ri -5 together represent an aromatic, heteroaromatic or aliphatic fused ring, with the proviso that at least one of the radicals Ri -3, and R 6 is a 4- r corresponds to sulfonate group.
Yi und Y2 bedeuten unabhängig voneinander gleiche oder unterschiedliche verbrückende, zwei- oder dreibindige Strukturelemente aus der Gruppe {Sauerstoff, Schwefel, substituierter Stickstoff oder Phosphor, gegebenenfalls substituiertes Ci-3- Alkylen, -Vinylen, -Alkyliden oder Silaalkylen, gegebenenfalls substituiertes Arylen oder Heteroarylen, Carboxylat, Thiocarboxylat, N-substituiertes Carboxamid oder -imid, gegebenenfalls substituiertes Silan, Einfachbindung}, wobei der mittlere Ring aliphatischen, heteroaliphatischen, aromatischen oder heteroaromatischen Charakter haben kann;Yi and Y 2 are each independently identical or different bridging, di- or trivalent structural elements from the group {oxygen, sulfur, substituted nitrogen or phosphorus, optionally substituted Ci -3 - alkylene, -vinylene, alkylidene or silaalkylene, optionally substituted arylene or Heteroarylene, carboxylate, thiocarboxylate, N-substituted carboxamide or imide, optionally substituted silane, single bond}, wherein the middle ring may have aliphatic, heteroaliphatic, aromatic or heteroaromatic character;
Qi-4 bedeuten unabhängig voneinander gleiche oder unterschiedliche Reste aus der Gruppe {Wasserstoff, Methyl, lineares, verzweigtes oder cyclisches Alkyl, gegebenenfalls substituiert, Aryl, Heteroaryl, gegebenenfalls substituiert} oder Qi und Q2 oder Q3 und Q4 bilden zusammen einen Ring und stehen für ein verbrückendes Strukturelement aus der Gruppe {gegebenenfalls substituiertes Alkylen, verzweigtes Alkylen, cyclisches Alkylen, gegebenenfalls substituiertes Arylen oder Heteroarylen}
oder unabhängig voneinander für einen oder zwei polycyclische Reste, wie z.B. Norbornyl oder Adamantyl; Qi-4 können eine oder mehrere Sulfonsäure- bzw. Sulfonatgruppen tragen.Qi- 4 independently represent identical or different radicals from the group {hydrogen, methyl, linear, branched or cyclic alkyl, optionally substituted, aryl, heteroaryl, optionally substituted} or Qi and Q 2 or Q 3 and Q 4 together form a ring and represent a bridging structural element from the group {optionally substituted alkylene, branched alkylene, cyclic alkylene, optionally substituted arylene or heteroarylene} or independently of one another for one or two polycyclic radicals, such as norbornyl or adamantyl; Qi -4 may carry one or more sulfonic acid or sulfonate groups.
Typische Beispiele für Liganden sind mono- oder disulfonierte Diphosphine auf Basis der Grundgerüste von Anthracen, Acridin, 9,10-Dihydroacridin, 9,19-Dihydroanthracen, Xanthen, Phenoxathiin, Thianthren, Dibenzo-p-dioxin, Phenoxazin, Phenothiazin, 5,10-Dihydrophenazin, Carbazol, Dibenzofuran, Dibenzothiophen, (10,11-Dihydro-) Benzoxepin und -azepin, und die von diesen abgeleiteten heterocyclischen Analoga.Typical examples of ligands are mono- or disulfonated diphosphines based on the basic skeletons of anthracene, acridine, 9,10-dihydroacridine, 9,19-dihydroanthracene, xanthene, phenoxathiin, thianthrene, dibenzo-p-dioxin, phenoxazine, phenothiazine, 5,10 Dihydrophenazine, carbazole, dibenzofuran, dibenzothiophene, (10,11-dihydro-) benzoxepine and -azepin, and the heterocyclic analogs derived therefrom.
In einer bevorzugten Ausführungsform steht Yi für eine gegebenenfalls substituierte Alkylengruppe, Alkyliden-, Vinyliden- oder Vinylengruppe und Y2 steht für O und jeweils einer der Reste R1-R3 und R4-R6 für eine Sulfonatgruppe. Für den Fall, dass Y1 für -C(CH3)2- und R2=R5=Sulfonat steht, ist entweder mindestens ein weiterer der Reste Ri-3 und R4-6 nicht Wasserstoff oder höchstens drei der Gruppen Qi-4 stehen für Phenyl.In a preferred embodiment Yi is an optionally substituted alkylene group, alkylidene, vinylidene or vinylene group and Y2 is O and in each case one of the radicals R 1 -R 3 and R 4 -R 6 is a sulfonate group. In the event that Y1 is -C (CH 3 ) 2 - and R 2 = R 5 = sulfonate, either at least one further of the radicals Ri- 3 and R 4-6 is not hydrogen or at most three of the groups Qi -4 stand for phenyl.
In einer weiteren ebenfalls bevorzugten Ausführungsform ist Yi eine gegebenenfalls substituierte Silylen- oder Silaalkylengruppe und Y2=O, wobei jeweils einer der Reste R1-R3 und R4-R6 für eine Sulfonatgruppe steht.In a further likewise preferred embodiment, Y 1 is an optionally substituted silylene or silaalkylene group and Y 2 = O, where in each case one of the radicals R 1 -R 3 and R 4 -R 6 is a sulfonate group.
Ebenfalls bevorzugt sind Liganden in denen Yi ein Schwefelatom oder eine gegebenenfalls substituierte Thiaalkylengruppe und Y2=O ist und jeweils einer der Reste RrR3 und R4-R6 einer Sulfonatgruppe entspricht. Ferner bevorzugte Ausführungsformen sind solche, in denen Yi eine Einfachbindung und Y2=O bedeutet und jeweils einer der Reste R1-R3 und R4-R6 einer Sulfonatgruppe entspricht, sowie solche in denen Yi ein substituiertes Stickstoffatom oder eine N-substituierte Azaalkylengruppe und Y2=O bedeutet und jeweils einer der Reste R1-R3 und R4-R6 einer Sulfonatgruppe entspricht und solche vorstehend genannten Liganden in denen Yi anstelle von Sauerstoff Schwefel bedeutet.Also preferred are ligands in which Yi is a sulfur atom or an optionally substituted thiaalkylene group and Y 2 = O and in each case one of the radicals RrR 3 and R 4 -R 6 corresponds to a sulfonate group. Further embodiments, preferred are those in which Yi is a single bond and Y 2 = O and one of the radicals R1-R 3, and R 4 -R 6 corresponds to a sulfonate group as well as those in which Yi is a substituted nitrogen atom or an N-substituted Azaalkylengruppe and Y 2 = O and in each case one of the radicals R 1 -R 3 and R 4 -R 6 corresponds to a sulphonate group and those abovementioned ligands in which Y 1 denotes sulfur instead of oxygen.
Die erfindungsgemäßen Liganden werden bei Verfahren zur Kreuzkupplung von aromatischen Verbindungen in Verbindung mit einem Übergangsmetallkatalysator eingesetzt.
Die Erfindung betrifft daher weiterhin neue Katalysatorsysteme enthaltend mindestens einen Liganden der folgenden FormelThe ligands according to the invention are used in processes for the cross-coupling of aromatic compounds in conjunction with a transition metal catalyst. The invention therefore further relates to novel catalyst systems comprising at least one ligand of the following formula
sowie mindestens ein Salz, einen Komplex oder eine metallorganische Verbindung eines Metalls der Gruppe {Mn, Fe, Co, Ni, Cu, Rh, Pd, Ir, Pt}, bevorzugt Palladium oder Nickel. Die Symbole R 1-6, Xi-io, Y 1+2 und Qi-4 haben die vorstehend genannte Bedeutung.and at least one salt, a complex or an organometallic compound of a metal of the group {Mn, Fe, Co, Ni, Cu, Rh, Pd, Ir, Pt}, preferably palladium or nickel. The symbols R 1-6 , Xi-io, Y 1 + 2 and Qi -4 have the abovementioned meaning.
Das Metall kann in beliebiger Oxidationsstufe vorliegen. Erfindungsgemäß wird es in Kreuzkupplungsreaktionen im Verhältnis zum Reaktanden (I) in Mengen von 0,001 Mol-% bis 100 Mol-%, bevorzugt zwischen 0.01 und 10 Mol-%, besonders bevorzugt zwischen 0,01 und 1 Mol-% eingesetzt.The metal can be present in any oxidation state. According to the invention, it is used in cross-coupling reactions in relation to the reactant (I) in amounts of 0.001 mol% to 100 mol%, preferably between 0.01 and 10 mol%, particularly preferably between 0.01 and 1 mol%.
Der Katalysator kann in fertiger Form zugesetzt werden oder sich in situ bilden, z.B. aus einem Präkatalysator durch Reduktion oder Hydrolyse oder aus einem Metallsalz und zugesetztem Liganden durch Komplexbildung.The catalyst can be added in finished form or form in situ, e.g. from a precatalyst by reduction or hydrolysis or from a metal salt and added ligand by complex formation.
Das erfindungsgemäße Katalysatorsystem ist, wie nachfolgend verdeutlicht werden soll, beispielsweise für folgende Kreuzkupplungsreaktionen einsetzbar:The catalyst system of the invention is, as will be clarified below, for example, for the following cross-coupling reactions used:
A) Ein Verfahren zur Herstellung von gemischten Aryl- und Heteroarylaminen sowie aryl- bzw. heteroarylsubstituierten Alkyl-/Arylethern (III) durch Kreuzkupplung von primären oder sekundären Alkyl- bzw. Arylaminen, Alkoholen bzw. Phenolen (II) mit Aryl- oder Heteroarylhalogeniden oder -sulfonaten (I). Bei Verwendung des erfindungsgemäßen Katalysatorsystems können bereits mit geringen Katalysatorbeladungen hohe Ausbeuten erzielt werden (Gleichung 1), welches sich durch folgende Vorteile auszeichnet:
• Sehr hohe Katalysatoraktivitäten, da der Ligand in der Reaktionsmischung als Anion vorliegt und besondere elektronische Effekte aufweist.A) A process for preparing mixed aryl and heteroarylamines and aryl- or heteroaryl-substituted alkyl / aryl ethers (III) by cross-coupling of primary or secondary alkyl or arylamines, alcohols or phenols (II) with aryl or heteroaryl halides or sulfonates (I). When using the catalyst system according to the invention high yields can be achieved even with low catalyst loadings (equation 1), which is characterized by the following advantages: • Very high catalyst activity, as the ligand is an anion in the reaction mixture and has special electronic effects.
• Einfache Abtrennung des Liganden sowie Metalls vom Produkt durch wässrige Extraktion.• Easy separation of the ligand and metal from the product by aqueous extraction.
• Die Reaktion kann auch in protischen Lösungsmitteln wie z.B. substituierten Alkoholen durchgeführt werden.The reaction can also be carried out in protic solvents, e.g. substituted alcohols are carried out.
• Die Struktur des Liganden ist in Abhängigkeit vom gewählten Grundkörper variabel und kann unterschiedlichen Bedürfnissen angepasst werden. • Abhängig vom gewählten Liganden kann der Bisswinkel und Abstand der beiden Phosphingruppen variiert werden, um die Wirksamkeit des Katalysators zu optimieren.• The structure of the ligand is variable depending on the chosen body and can be adapted to different needs. • Depending on the ligand selected, the bite angle and spacing of the two phosphine groups can be varied to optimize the efficiency of the catalyst.
• Aufgrund der hohen Aktivität der Katalysatorsysteme können kostengünstige Basen (Alkalihydroxide, -carbonate) verwendet werden.Due to the high activity of the catalyst systems, inexpensive bases (alkali hydroxides, carbonates) can be used.
I Il IIII Il III
GLEICHUNG 1EQUATION 1
Dabei steht HaI für Chlor, Brom oder lod oder für Sulfonate wie beispielsweise Trifluormethansulfonat (Triflat), Nonafluortrimethylmethansulfonat (Nonaflat), Methansulfonat, Benzolsulfonat, para-Toluolsulfonat oder auch Methoxy. Xi-5 bedeuten unabhängig voneinander Kohlenstoff oder die Gruppe XjR1 steht für Stickstoff, oder jeweils zwei benachbarte über eine formale Doppelbindung verbundene XiRj stehen gemeinsam für O (Furane), S (Thiophene), NH oder NRj (Pyrrole).Here, Hal is chlorine, bromine or iodine or sulfonates such as trifluoromethanesulfonate (triflate), Nonafluortrimethylmethansulfonat (nonaflate), methanesulfonate, benzenesulfonate, para-toluenesulfonate or methoxy. Xi -5 independently represent carbon or the group Xjr 1 is nitrogen, or in each case two adjacent via a formal double bond together are connected XiRj O (furans), S (thiophenes), NH or NRj (pyrroles).
Bevorzugte Verbindungen der Formel (I), die mit dem erfindungsgemäßen Katalysatorsystem nach diesem Verfahren umgesetzt werden können, sind z.B. Benzole, Pyridine, Pyrimidine, Pyrazine, Pyridazine, Furane, Thiophene, Pyrrole, beliebig N-substituierte Pyrrole oder Naphthaline, Chinoline, Indole, Benzofurane usw.
Die Reste Ri-5 in Gleichung 1 stehen für Substituenten aus der Gruppe {Wasserstoff, Methyl, primäre, sekundäre oder tertiäre, cyclische oder acyclische Alkylreste mit 2 bis 20 C-Atomen, bei denen gegebenenfalls ein oder mehrere Wasserstoffatome durch Fluor oder Chlor oder Brom ersetzt sind, z.B. CF3, substituierte cyclische oder acyclische Alkylgruppen, Hydroxy, Alkoxy, Amino, Alkylamino, Dialkylamino, Arylamino, Diarylamino, Alkylarylamino, Pentafluorsulfuranyl, Phenyl, substituiertes Phenyl, Heteroaryl, substituiertes Heteroaryl, Thio, Alkylthio, Arylthio, Diarylphosphino, Dialkylphosphino, Alkylarylphosphino, gegebenenfalls substituiertes Aminocarbonyl, CO2 ", Alkyl- oder Aryloxycarbonyl, Hydroxyalkyl, Alkoxyalkyl, Fluor oder Chlor, Nitro, Cyano, Aryl- oder Alkylsulfon, Aryl- oder Alkylsulfonyl}, oder es können jeweils zwei benachbarte Reste Ri-5 zusammen einem aromatischen, heteroaromatischen oder aliphatischen ankondensierten Ring entsprechen.Preferred compounds of the formula (I) which can be reacted with the catalyst system according to the invention by this process are, for example, benzenes, pyridines, pyrimidines, pyrazines, pyridazines, furans, thiophenes, pyrroles, N-substituted pyrroles or naphthalenes, quinolines, indoles, Benzofurans etc. The radicals Ri -5 in Equation 1 are substituents from the group {hydrogen, methyl, primary, secondary or tertiary, cyclic or acyclic alkyl radicals having 2 to 20 C atoms, in which optionally one or more hydrogen atoms by fluorine or chlorine or bromine substituted, for example CF 3 , substituted cyclic or acyclic alkyl groups, hydroxy, alkoxy, amino, alkylamino, dialkylamino, arylamino, diarylamino, alkylarylamino, pentafluorosulfurane, phenyl, substituted phenyl, heteroaryl, substituted heteroaryl, thio, alkylthio, arylthio, diarylphosphino, dialkylphosphino , Alkylarylphosphino, optionally substituted aminocarbonyl, CO 2 " , alkyl or aryloxycarbonyl, hydroxyalkyl, alkoxyalkyl, fluorine or chlorine, nitro, cyano, aryl or alkylsulfone, aryl or alkylsulfonyl}, or in each case two adjacent radicals Ri -5 together an aromatic, heteroaromatic or aliphatic fused ring correspond.
Für Z = O kann R' für gleiche oder unterschiedliche Reste aus der Gruppe {Wasserstoff, Methyl, lineares, verzweigtes C1-C2O Alkyl oder cyclisches Alkyl, substituiertes oder unsubstituiertes Phenyl} stehen.For Z = O, R 'may be the same or different radicals from the group {hydrogen, methyl, linear, branched C 1 -C 20 alkyl or cyclic alkyl, substituted or unsubstituted phenyl}.
Für Z = NR" können R' und R" unabhängig voneinander für gleiche oder unterschiedliche Reste aus der Gruppe {Wasserstoff, Methyl, lineares, verzweigtes C1-C20 Alkyl oder cyclisches Alkyl, substituiertes oder unsubstituiertes Phenyl} stehen oder zusammen einen Ring bilden und aus der Gruppe {gegebenenfalls substituiertes Alkylen, verzweigtes Alkylen, cyclisches Alkylen, substituiertes Azaalkylen, substituiertes Oxaalkylen, substituiertes Phosphaalkylen oder gegebenenfalls substituiertes Sulfaalkylen} stammen.For Z = NR ", R 'and R" independently of one another may stand for identical or different radicals from the group {hydrogen, methyl, linear, branched C 1 -C 20 alkyl or cyclic alkyl, substituted or unsubstituted phenyl} or together form a ring and from the group {optionally substituted alkylene, branched alkylene, cyclic alkylene, substituted azaalkylene, substituted oxaalkylene, substituted phosphaalkylene or optionally substituted sulfaalkylene}.
Typische Beispiele für die Verbindung Il in Gleichung 1 sind damit Methyl-, Ethyl-, 1-Methylethyl-, Propyl-, 1-Methylpropyl-, 2-Methylpropyl-, 1 ,1-Dimethylethyl-, Butyl- und Pentylamin, Cyclopropyl-, Cyclobutyl-, Cyclopentyl-, Cyclohexylamin, Phenyl-, Benzylamin.Typical examples of the compound II in Equation 1 are thus methyl, ethyl, 1-methylethyl, propyl, 1-methylpropyl, 2-methylpropyl, 1, 1-dimethylethyl, butyl and pentylamine, cyclopropyl, Cyclobutyl, cyclopentyl, cyclohexylamine, phenyl, benzylamine.
B) Weiterhin können die erfindungsgemäßen Katalysatorsysteme in Verfahren zur Knüpfung von C-C-Bindungen durch Umsetzung von Aryl- oder Heteroarylhalogeniden und -sulfonaten (I) mit organischen Verbindungen des Bors, Magnesiums, Zinks und Zinns sowie des Siliciums (IV) eingesetzt werden. Im Falle des Einsatzes von
Organoborverbindungen ist der Zusatz einer Bronsted-Base in einem Lösungsmittel oder Lösungsmittelgemisch sinnvoll. Auch hier können durch Verwendung der erfindungsgemäßen Katalysatorsysteme mit geringen Katalysatorbeladungen hohe Ausbeuten erzielt werden (Gleichung 2). Im Unterschied zum Verfahren A) bietet dieses Verfahren zusätzlich die Möglichkeit, in wässrigen Lösungsmittelsystemen zu arbeiten.B) Furthermore, the catalyst systems of the invention can be used in processes for the formation of C-C bonds by reacting aryl or heteroaryl halides and sulfonates (I) with organic compounds of boron, magnesium, zinc and tin and of silicon (IV). In case of use of Organoboron compounds, the addition of a Bronsted base in a solvent or solvent mixture makes sense. Again, high yields can be achieved by using the catalyst systems of the invention with low catalyst loadings (Equation 2). In contrast to method A), this method additionally offers the possibility of working in aqueous solvent systems.
I IV VI IV V
GLEICHUNG 2EQUATION 2
Dabei haben HaI und X1-X5 sowie R1-R5 die unter A) beschriebenen Bedeutungen.Here, Hal and X 1 -X 5, and R1-R5 are as described under A).
M steht für Bor, Magnesium, Zink, Silicium oder Zinn. Für M=Bor gilt (n+m)=3 oder bei Anwesenheit eines Gegenkations (n+m)=4 (Borate), für M=Magnesium oder Zink gilt (n+m)=2 oder bei Anwesenheit eines Gegenkations (n+m)=3 (Magnesate, Zinkate), für M=Zinn oder Silicium gilt (n+m)=4 (Stannane, Silane, Siloxane).M is boron, magnesium, zinc, silicon or tin. For M = boron, (n + m) = 3 or in the presence of a counter cation (n + m) = 4 (borates), for M = magnesium or zinc, (n + m) = 2 or in the presence of a counter cation (n + m) = 3 (magnesates, zincates), for M = tin or silicon, (n + m) = 4 (stannanes, silanes, siloxanes).
R' kann für je einen von insgesamt n gleichen oder unterschiedlichen Resten aus der Gruppe { Methyl, lineares, verzweigtes oder cyclisches substituiertes oder unsubstituiertes CrC^o-Alkyl, Vinyl oder Alkinyl, substituiertes oder unsubstituiertes Aryl oder Heteroaryl} stehen.R 'may each represent one of a total of n identical or different radicals from the group {methyl, linear, branched or cyclic substituted or unsubstituted C 1 -C 20 -alkyl, vinyl or alkynyl, substituted or unsubstituted aryl or heteroaryl}.
R" kann für M=Bor für je einen von insgesamt m gleichen oder unterschiedlichen Resten aus der Gruppe { Methyl, lineares, verzweigtes Ci-C2o-Alkyl oder cyclisches substituiertes oder unsubstituiertes Alkyl, Vinyl oder Alkinyl; Hydroxy, lineares, verzweigtes oder cyclisches substituiertes oder unsubstituiertes CrC2o-Alkoxy sowie Dialkylamino} stehen, wobei zwei oder mehrere dieser R" miteinander verknüpft sein und einen oder mehrere Ringe bilden können; außerdem kann R" für einen über O-B- angebundenen Rest R' stehen (Boronsäureanhydride).
R" kann für M=Zinn für je einen von insgesamt m gleichen oder unterschiedlichen Resten aus der Gruppe {Methyl, lineares, verzweigtes C1-C2O-AIKyI oder cyclisches substituiertes oder unsubstituiertes Alkyl, Vinyl oder Alkinyl} stehen. R" kann für M=Silicium für je einen von insgesamt m gleichen oder unterschiedlichen Resten aus der Gruppe {Methyl, Methoxy, lineares, verzweigtes Ci-C2o-Alkyl oder -Alkoxy, cyclisches substituiertes oder unsubstituiertes Alkyl, Alkoxy, Vinyl oder Alkinyl} stehen.R "can, for M = boron, in each case one of a total of m identical or different radicals from the group {methyl, linear, branched C 1 -C 20 -alkyl or cyclic substituted or unsubstituted alkyl, vinyl or alkinyl, hydroxy, linear, branched or cyclic substituted or unsubstituted C r C 2 o-alkoxy and dialkylamino}, wherein two or more of these R "may be linked together and form one or more rings; In addition, R can stand for an O-linked radical R '(Boronsäureanhydride). R "may for M = tin for each are a total of m identical or different radicals from the group {methyl, linear, branched C 1 -C 2O -alkyl or cyclic substituted or unsubstituted alkyl, vinyl or alkinyl}. R" can be used for M = silicon for each one of a total of m identical or different radicals from the group {methyl, methoxy, linear, branched Ci-C 2 o-alkyl or alkoxy, cyclic substituted or unsubstituted alkyl, alkoxy, vinyl or alkynyl}.
R" kann für M=Magnesium und M=Zink für je einen von insgesamt m gleichen oder unterschiedlichen Resten der Gruppe {Fluor, Chlor, Brom, lod} stehen.R "may stand for M = magnesium and M = zinc for any one of a total of m identical or different radicals of the group {fluorine, chlorine, bromine, iodine}.
Typische Beispiele für die Verbindung (IV) sind damit Aryl- oder Heteroarylboronsäuren und -borinsäuren (z.B. 3-Fluorphenylboronsäure) und ihre Ester (z.B. 4-Aminophenylboronsäurepinakolester), Tetraarylboranate, Vinylboronsäure, Butylboronsäure, Arylmagnesiumhalogenide (z.B. Phenylmagnesiumchlorid), Diarylmagnesiumverbindungen und Triarylmagnesate, die analogen Alkyl- und Arylzinkverbindungen, Vinyl-, Alkinyl- und Aryltrialkylstannane und -silane sowie -siloxane.Typical examples of compound (IV) are thus aryl or heteroaryl boronic acids and borinic acids (eg 3-fluorophenylboronic acid) and their esters (eg 4-aminophenylboronic acid pinacol ester), tetraarylboranates, vinylboronic acid, butylboronic acid, arylmagnesium halides (eg phenylmagnesium chloride), diarylmagnesium compounds and triarylmagnesates analogous alkyl and aryl zinc compounds, vinyl, alkynyl and aryl trialkyl stannanes and silanes and siloxanes.
C) In einer weiteren Ausführungsform kann das erfindungsgemäße Katalysatorsystem zur Knüpfung von C-C-Bindungen durch Umsetzung von Aryl- oder Heteroarylhalogeniden und -sulfonaten (I) mit Alkenen (VI) eingesetzt werden (Gleichung 3). Wie bei Verfahren B) besteht auch bei diesem Verfahren vorteilhafterweise zusätzlich die Möglichkeit, in wässrigen Lösungsmittelsystemen zu arbeiten.C) In another embodiment, the catalyst system according to the invention for the formation of C-C bonds by reaction of aryl or heteroaryl halides and sulfonates (I) with alkenes (VI) can be used (equation 3). As in process B), it is also advantageously possible to work in aqueous solvent systems in this process as well.
GLEICHUNG 3EQUATION 3
Dabei können HaI und X1-X5 sowie RrR5 die unter A) beschriebenen Bedeutungen haben.
R', R" und R1" können unabhängig voneinander für Wasserstoff oder beliebige organische und elementorganische Substituenten, d.h. Substituenten, die über Heteroatome angebracht sind, z.B. R1O-, R'S-, R'COO- usw., stehen, wobei zwei oder mehrere dieser Reste miteinander verknüpft sein und einen oder mehrere Ringe bilden können.Here, Hal and X 1 -X 5 and RrR 5 may have the meanings described under A). R ', R "and R 1 " may be independently hydrogen or any organic and elemental organic substituents, ie, substituents attached via heteroatoms, eg, R 1 O-, R'S-, R'COO-, etc., wherein two or more of these radicals may be linked together and form one or more rings.
Typische Beispiele für die Verbindung (VI) sind damit Acrylate, offenkettige und cyclische Alkene, Styrole, ebenso Enamine oder Enamide.Typical examples of the compound (VI) are thus acrylates, open-chain and cyclic alkenes, styrenes, as well as enamines or enamides.
D) In einer weiteren bevorzugten Ausführungsform können die erfindungsgemäßen Katalysatorsysteme in Kreuzkupplungsverfahren zur Knüpfung von C-C-Bindungen durch Umsetzung von Aryl- oder Heteroarylhalogeniden und -sulfonaten (I) mit terminalen Alkinen (VIII) eingesetzt werden (Gleichung 4). Auch hier werden wieder die vorstehend genannten Vorteile erzielt.D) In a further preferred embodiment, the catalyst systems of the invention can be used in cross-coupling processes for the formation of C-C bonds by reacting aryl or heteroaryl halides and sulfonates (I) with terminal alkynes (VIII) (Equation 4). Again, the above advantages are achieved again.
I VIII IXI VIII IX
GLEICHUNG 4EQUATION 4
HaI und X1-X5 sowie R1-R5 haben die unter a) beschriebenen Bedeutungen.Hal and X 1 -X 5 and also R 1 -R 5 have the meanings described under a).
R' kann für Wasserstoff oder beliebige organische und elementorganische Substituenten stehen.R 'may be hydrogen or any organic and organoelement substituents.
Typische Beispiele für die Verbindung (VIII) sind damit Acetylen, aliphatische Alkine, Arylalkine und Alkinylether.Typical examples of the compound (VIII) are thus acetylene, aliphatic alkynes, arylalkynes and alkynyl ethers.
E) In einer weiteren bevorzugten Ausführungsform können die erfindungsgemäßenE) In a further preferred embodiment, the inventive
Katalysatorsysteme in Kreuzkupplungsverfahren zur Herstellung von 2-Aryl- oder Heteroarylcarbonyl- bzw. -nitrilverbindungen (Xl) durch Kreuzkupplung von
enolisierbaren Carbonylverbindungen, Nitrilen und ihren Analoga (X) mit substituierten Aryl- oder Heteroarylverbindungen (I) eingesetzt (Gleichungen 5a und 5b), welches sich ebenfalls durch vorstehend genannten Vorteile auszeichnet.Catalyst systems in cross-coupling process for the preparation of 2-aryl or heteroarylcarbonyl or -nitrilverbindungen (Xl) by cross-coupling of enolisable carbonyl compounds, nitriles and their analogs (X) with substituted aryl or heteroaryl compounds (I) used (equations 5a and 5b), which is also distinguished by the advantages mentioned above.
I Xa XIaI Xa Xia
GLEICHUNG 5aEQUATION 5a
I Xb XIbI Xb XIb
GLEICHUNG 5bEQUATION 5b
HaI und X1-X5 sowie R1-R5 haben die unter A) beschriebenen Bedeutungen.Hal and X 1 -X 5 and R 1 -R 5 have the meanings described under A).
Z (Gleichung 5a) steht für O, S, NR'", NOR'" (geschütztes Oxim), NNR111R"" (doppelt geschütztes Hydrazon) (Gleichung 5a) oder mit W zusammen für N allein (Gleichung 5b).Z (Equation 5a) represents O, S, NR ''',NOR''(protected oxime), NNR 111 R''' (double protected hydrazone) (Equation 5a) or with W together for N alone (Equation 5b).
Für Z = O oder S können R', R" für gleiche oder unterschiedliche Reste aus der Gruppe {Wasserstoff, Methyl, lineares, verzweigtes Ci-C2oAlkyl oder cyclisches, gegebenenfalls substituiertes Alkyl, substituiertes oder unsubstituiertes Aryl- oder Heteroaryl oder eine nicht an der Reaktion teilnehmende funktionelle Gruppe, z.B. Carbonyl, Carboxyl, N-substituiertes Imin oder Nitril} stehen oder zusammen einen Ring bilden. R', R" können unabhängig voneinander für gleiche oder unterschiedliche Reste aus der Gruppe {Wasserstoff, Methyl, lineares, verzweigtes C1-C20 Alkyl oder cyclisches, gegebenenfalls substituiertes Alkyl, substituiertes oder unsubstituiertes Aryl- oder
Heteroaryl oder eine nicht an der Reaktion teilnehmende funktionelle Gruppe, z.B. Carbonyl, Carboxyl, N-substituiertes Imin oder Nitril} stehen oder zusammen oder mit W, R'" oder R"" einen Ring bilden.For Z = O or S, R ', R "may represent identical or different radicals from the group {hydrogen, methyl, linear, branched C 1 -C 20 -alkyl or cyclic, optionally substituted alkyl, substituted or unsubstituted aryl or heteroaryl or one not on Reaction participating functional group, for example carbonyl, carboxyl, N-substituted imine or nitrile} or together form a ring R ', R "can independently for identical or different radicals from the group {hydrogen, methyl, linear, branched C 1 -C 20 alkyl or cyclic, optionally substituted alkyl, substituted or unsubstituted aryl or Heteroaryl or a non-participating in the reaction functional group, for example, carbonyl, carboxyl, N-substituted imine or nitrile} or together or with W, R '"or R""form a ring.
Für Z = NR1", NOR'", NNR111R"" können R1" und R"" unabhängig voneinander für gleiche oder unterschiedliche Reste aus der Gruppe {Methyl, lineares, verzweigtes Ci-C2o-Alkyl oder cyclisches, gegebenenfalls substituiertes Alkyl, substituiertes oder unsubstituiertes Aryl- oder Heteroaryl oder eine nicht an der Reaktion teilnehmende funktionelle Gruppe, z.B. Carbonyl, Carboxyl, N-substituiertes Imin oder Nitril} stehen oder zusammen oder mit Woder mit R' oder R" einen Ring bilden.For Z = NR 1 ", NOR '", NNR 111 R "", R 1 "and R""can independently of one another represent identical or different radicals from the group {methyl, linear, branched C 1 -C 20 -alkyl or cyclic, optionally substituted alkyl, substituted or unsubstituted aryl or heteroaryl or a non-participating in the reaction functional group, for example carbonyl, carboxyl, N-substituted imine or nitrile} or together or with W or R 'or R "form a ring.
W steht für einen Rest aus der Gruppe {Wasserstoff, Methyl, lineares, verzweigtes Ci-C2o-Alkyl oder cyclisches, gegebenenfalls substituiertes Alkyl, substituiertes oder unsubstituiertes Aryl- oder Heteroaryl, gegebenenfalls substituiertes Alkoxy, Aryloxy, Heteraryloxy, gegebenenfalls substituiertes Alkylthio, Arylthio, Heteroarylthio, gegebenenfalls substituiertes Dialkylamino, Di(hetero)arylamino,W is a radical from the group {hydrogen, methyl, linear, branched C 1 -C 20 -alkyl or cyclic, optionally substituted alkyl, substituted or unsubstituted aryl or heteroaryl, optionally substituted alkoxy, aryloxy, heteraryloxy, optionally substituted alkylthio, Arylthio, heteroarylthio, optionally substituted dialkylamino, di (hetero) arylamino,
Alkyl(hetero)arylamino} und kann mit R1, R", R"1 oder R"" einen Ring bilden (Gleichung 5a). Z und W können zusammen für einen Nitrilstickstoff stehen (Gleichung 5b).Alkyl (hetero) arylamino} and can form a ring with R 1 , R ", R" 1 or R "" (equation 5a). Z and W together may represent a nitrile nitrogen (Equation 5b).
Typische Beispiele für die Verbindungen (Xa) und (Xb) in Gleichungen 5 a + b sind damit enolisierbare Ketone, Aldehyde, N-substituierte Imine, Thioketone, Carbonsäureester, Thiocarbonsäureester und Nitrile.Typical examples of the compounds (Xa) and (Xb) in equations 5 a + b are thus enolizable ketones, aldehydes, N-substituted imines, thioketones, carboxylic esters, thiocarboxylic esters and nitriles.
F) In einer weiteren bevorzugten Ausführungsform können die erfindungsgemäßen Katalysatorsysteme in Verfahren zur Herstellung von Aryl- oder Heteroarylnitrilen (XIII) durch Kreuzkupplung von Cyaniden (XII) mit substituierten Aryl- oder Heteroarylverbindungen (I) eingesetzt werden (Gleichung 6), welches sich ebenfalls durch die vorstehend genannten Vorteile auszeichnet.
F) In a further preferred embodiment, the catalyst systems of the invention can be used in processes for the preparation of aryl or heteroaryl nitriles (XIII) by cross-coupling of cyanides (XII) with substituted aryl or heteroaryl compounds (I) (Equation 6), which is also characterized by the advantages mentioned above are distinguished.
I XII XIIII XII XIII
GLEICHUNG 6EQUATION 6
HaI und X1-X5 sowie R1-R5 die unter A) beschriebenen Bedeutungen haben.Hal and X1-X5 and R1-R5 have the meanings described under A).
MCN steht für NaCN, KCN, Zn(CN)2, K3[Fe(CN)6], K4[Fe(CN)6], HCN oder ein Cyanhydrin.MCN stands for NaCN, KCN, Zn (CN) 2 , K 3 [Fe (CN) 6 ], K 4 [Fe (CN) 6 ], HCN or a cyanohydrin.
Der Zusatz von Bronsted-Basen zum Reaktionsgemisch ist in allen vorstehend beschriebenen Verfahren A) bis F) - außer im Fall B) beim Einsatz von Magnesium-, Zink- und Zinnverbindungen - notwendig, um akzeptable Reaktionsgeschwindigkeiten zu erzielen. Als Basen gut geeignet sind Hydroxide, Carbonate und Fluoride der Alkali- und Erdalkalimetalle, Carbonate, Hydrogencarbonate, Amide und Phosphate der Alkalimetalle und ihre Gemische sowie aliphatische Amine und andere organische Stickstoffbasen wie Pyridine und DBU. Besonders geeignet für die unter A) und E) beschriebenen Anwendungen sind die Basen der Gruppe {Kalium-tert-butylat, Natrium- tert-butylat, Cäsium-tert-butylat, Lithium-tert-butylat}; besonders geeignet für die übrigen Anwendungen sind die Basen der Gruppe {Triethylamin, Natriumcarbonat, Kaliumcarbonat, Cäsiumcarbonat, Kaliumphosphat, Cäsiumfluorid, Kaliumfluorid, Bariumhydroxid}. Dabei wird üblicherweise mindestens die Stoffmenge an Base eingesetzt, die der Stoffmenge des zu kuppelnden Nucleophils entspricht, zumeist werden 1.0 bis 6 Äquivalente, vorzugsweise 1.2 bis 3 Äquivalente an Base bezogen auf das zu kuppelnde Nucleophil eingesetzt.The addition of Bronsted bases to the reaction mixture is necessary in all the processes A) to F) described above-except in case B) when using magnesium, zinc and tin compounds-in order to achieve acceptable reaction rates. Suitable bases are hydroxides, carbonates and fluorides of the alkali and alkaline earth metals, carbonates, bicarbonates, amides and phosphates of the alkali metals and their mixtures, and aliphatic amines and other organic nitrogen bases such as pyridines and DBU. Particularly suitable for the applications described under A) and E) are the bases of the group {potassium tert-butoxide, sodium tert-butoxide, cesium tert-butylate, lithium tert-butylate}; Particularly suitable for the other applications are the bases of the group {triethylamine, sodium carbonate, potassium carbonate, cesium carbonate, potassium phosphate, cesium fluoride, potassium fluoride, barium hydroxide}. In this case, usually at least the amount of base is used which corresponds to the molar amount of the nucleophile to be coupled, usually 1.0 to 6 equivalents, preferably 1.2 to 3 equivalents of base based on the nucleophile to be coupled used.
Sämtliche vorstehend beschriebenen Reaktionen A) bis F) werden in einem geeigneten Lösungsmittel oder einem ein- oder mehrphasigen Lösungsmittelgemisch durchgeführt, das ein hinreichendes Lösevermögen für alle beteiligten Reaktanden hat. Gut geeignet sind offenkettige und cyclische Ether und Diether, Oligo- und Polyether sowie substituierte einfache oder mehrfache Alkohole und gegebenenfalls substituierte
Aromaten, außerdem polare aprotische Lösungsmittel. Besonders bevorzugt werden Gemische mehrerer Lösungsmittel der Gruppe {Diglyme, substituierte Glymes, 1 ,4-Dioxan, Isopropanol, tert-Butanol, 2,2-Dimethyl-1-propanol, Toluol, XyIoI, Ethylenglycol, Tetrahydrofuran, 2-Methyltetrahydrofuran, Methanol, Ethanol, Propanol, Isopropanol, Dimethylsulfoxid, Dimethylformamid, N-Methylpyrrolidon, Acetonitril, Propionitril} eingesetzt. Im Falle der Kupplung von Organoborverbindungen in Anwendung B) ist Wasser ebenfalls ein bevorzugtes Lösungsmittel. Die Reaktion kann bei Temperaturen zwischen -30 0C und dem Siedepunkt des verwendeten Lösungsmittels beim verwendeten Druck durchgeführt werden. Um eine schnellere Reaktion zu erzielen, ist die Durchführung bei erhöhten Temperaturen im Bereich von -20 bis 2400C bevorzugt. Besonders bevorzugt ist der Temperaturbereich von 0 bis 1500C.All reactions A) to F) described above are carried out in a suitable solvent or a single- or multi-phase solvent mixture which has sufficient dissolving power for all the reactants involved. Well-suited are open-chain and cyclic ethers and diethers, oligo- and polyethers as well as substituted single or multiple alcohols and optionally substituted ones Aromatics, as well as polar aprotic solvents. Particular preference is given to mixtures of a plurality of solvents from the group {diglyme, substituted glymes, 1,4-dioxane, isopropanol, tert-butanol, 2,2-dimethyl-1-propanol, toluene, xylene, ethylene glycol, tetrahydrofuran, 2-methyltetrahydrofuran, methanol, Ethanol, propanol, isopropanol, dimethyl sulfoxide, dimethylformamide, N-methylpyrrolidone, acetonitrile, propionitrile} used. In the case of the coupling of organoboron compounds in application B), water is also a preferred solvent. The reaction can be carried out at temperatures between -30 0 C and the boiling point of the solvent used at the pressure used. In order to achieve a faster reaction, the implementation at elevated temperatures in the range of -20 to 240 0 C is preferred. Particularly preferred is the temperature range from 0 to 150 0 C.
Ganz besonders bevorzugt ist der Temperaturbereich von 20 bis 130 °C für die Anwendungen A), D), E), F), von -20 bis 700C beim Einsatz von Magnesium- und Zinkverbindung in Anwendung B), von 20 bis 1300C beim Einsatz von Bor- und Zinnverbindungen in Anwendung B) und von 50 bis 1800C für die Anwendung C).Most preferably, the temperature range of 20 to 130 ° C for the applications A), D), E), F), from -20 to 70 0 C when using magnesium and zinc compound in application B), from 20 to 130 0 C when using boron and tin compounds in application B) and from 50 to 180 0 C for the application C).
Die Konzentration der Reaktanden kann in weiten Bereichen variiert werden. Zweckmäßigerweise wird die Reaktion in einer möglichst hohen Konzentration durchführt, wobei die Löslichkeiten der Reaktionspartner und Reagentien im jeweiligen Reaktionsmedium beachtet werden müssen. Bevorzugt wird die Reaktion im Bereich zwischen 0.05 und 5 mol/l bezogen auf den im Unterschuss vorliegenden Reaktanden durchgeführt.The concentration of the reactants can be varied within wide limits. Conveniently, the reaction is carried out in the highest possible concentration, wherein the solubilities of the reactants and reagents must be observed in the particular reaction medium. The reaction is preferably carried out in the range from 0.05 to 5 mol / l, based on the reactant present in the deficit.
Nucleophiler Reaktionspartner (II), (IV), (VI), (VII) bzw. (X) und elektrophiler Reaktionspartner (I) können in Molverhältnissen von 10:1 bis 1 :10 eingesetzt werden, bevorzugt sind Verhältnisse von 3:1 bis 1 :3 und besonders bevorzugt sind Verhältnisse von 1.2:1 bis 1 :1.2.Nucleophilic reactants (II), (IV), (VI), (VII) or (X) and electrophilic reactants (I) can be used in molar ratios of 10: 1 to 1:10, preferably ratios of 3: 1 to 1: 3 and particularly preferred are ratios of 1.2: 1 to 1: 1.2.
In einer der bevorzugten Ausführungsformen werden alle Materialien vorgelegt und das Gemisch unter Rühren auf Reaktionstemperatur erhitzt. In einer weiteren bevorzugten Ausführungsform, die sich besonders für die Anwendung im großen Maßstab eignet, wird das Nucleophil und gegebenenfalls weitere Reaktanden während der Reaktion zum Reaktionsgemisch dosiert.
Die Aufarbeitung erfolgt üblicherweise mit einem Gemisch aus aromatischen Kohlenwasserstoffen und Wasser unter Abtrennung der wässrigen Phase, die die anorganischen Bestandteile sowie Ligand und Übergangsmetall aufnimmt, wobei das Produkt in der organischen Phase verbleibt, wenn nicht vorhandene saure Funktionsgruppen zu einem abweichenden Phasenverhalten führen. Gegebenenfalls können ionische Flüssigkeiten zur Abtrennung der polareren Bestandteile eingesetzt werden. Das Produkt wird bevorzugt durch Fällung oder Destillation aus der organischen Phase isoliert, z.B. durch Einengen oder durch Zusatz von Fällungsmitteln. Häufig ist eine zusätzliche Reinigung z.B. durch Umkristallisation oder Chromatographie unnötig. Die isolierten Ausbeuten liegen meistens im Bereich von 70 bis 100 %, vorzugsweise im Bereich > 75 % bis 100 %, insbesondere > 80 % bis 100 %.In one of the preferred embodiments, all materials are initially charged and the mixture is heated with stirring to the reaction temperature. In a further preferred embodiment, which is particularly suitable for use on a large scale, the nucleophile and, if appropriate, further reactants are metered into the reaction mixture during the reaction. The workup is usually carried out with a mixture of aromatic hydrocarbons and water with removal of the aqueous phase, which absorbs the inorganic constituents and ligand and transition metal, the product remaining in the organic phase, if non-existent acidic functional groups lead to a different phase behavior. Optionally, ionic liquids can be used to separate the more polar constituents. The product is preferably isolated by precipitation or distillation from the organic phase, for example by concentration or by addition of precipitants. Frequently, additional purification, for example by recrystallization or chromatography, is unnecessary. The isolated yields are usually in the range of 70 to 100%, preferably in the range> 75% to 100%, in particular> 80% to 100%.
Das erfindungsgemäße Verfahren eröffnet eine vor allem in der wässrigen Aufarbeitung sehr ökonomische Methode, umThe inventive method opens up a very economical method, especially in the aqueous workup to
a) gemischte Aryl- und Heteroarylamine sowie aryl- bzw. heteroarylsubstituierte Alkyl-/Arylether ausgehend von den entsprechenden primären oder sekundären Alkyl- bzw. Arylaminen, Alkoholen bzw. Phenolen oder ihren Derivaten und den entsprechenden Aryl- oder Heteroarylhalogeniden oder -sulfonaten herzustellen; b) unsymmetrische Biaryle, Heterobiaryle und analoge Kupplungsprodukte ausgehend von den entsprechenden Aryl- bzw. Heteroarylhalogeniden und -sulfonaten, insbesondere den unreaktiven Chloriden, und den entsprechenden Borderivaten, insbesondere Boronsäuren, Magnesium-, Zink- und Zinnorganylen herzustellen; c) Aryl- und Heteroarylvinylverbindungen ausgehend von den entsprechenden Aryl- oder Heteroarylhalogeniden oder -sulfonaten und den entsprechenden Alkenen herzustellen; d) Aryl- und Heteroarylalkine ausgehend von den entsprechenden Aryl- oder Heteroarylhalogeniden oder -sulfonaten und den entsprechenden terminalena) produce mixed aryl and heteroarylamines and aryl or heteroaryl-substituted alkyl / aryl ethers starting from the corresponding primary or secondary alkyl or arylamines, alcohols or phenols or their derivatives and the corresponding aryl or heteroaryl halides or sulfonates; b) unsymmetrical biaryls, heterobiaryls and analogous coupling products starting from the corresponding aryl or heteroaryl halides and sulfonates, in particular the unreactive chlorides, and the corresponding boron derivatives, in particular boronic acids, magnesium, zinc and tin organyls; c) preparing aryl and heteroaryl vinyl compounds starting from the corresponding aryl or heteroaryl halides or sulfonates and the corresponding alkenes; d) aryl and heteroaryl alkynes starting from the corresponding aryl or heteroaryl halides or sulfonates and the corresponding terminal
Alkinen herzustellen, e) um in 2-Position arylierte bzw. heteroarylierte Carbonylverbindungen, ihre
Derivate und Analoga sowie Nitrile ausgehend von den entsprechenden Carbonylverbindungen bzw. ihren Derivaten und Nitrilen und den entsprechenden Aryl- oder Heteroarylhalogeniden oder -sulfonaten und f) Aryl- und Heteroarylnitrile ausgehend von den entsprechenden Aryl- oder Heteroarylhalogeniden und -sulfonaten herzustellen.To prepare alkynes; e) arylated or heteroarylated carbonyl compounds in the 2-position, their Derivatives and analogues and nitriles starting from the corresponding carbonyl compounds or their derivatives and nitriles and the corresponding aryl or heteroaryl halides or sulfonates; and f) aryl and heteroaryl nitriles starting from the corresponding aryl or heteroaryl halides and sulfonates.
Die Produkte fallen in hoher Reinheit und Ausbeute an, so dass auf aufwendigeThe products are obtained in high purity and yield, so that on consuming
Reinigungsprozeduren wie z.B. Chromatographie zumeist verzichtet werden kann.Cleaning procedures such as e.g. Chromatography can usually be dispensed with.
Außerdem bewirkt die Sulfonierung des Liganden in den meisten Fällen eine deutliche Beschleunigung der Reaktion gegenüber der Verwendung des unsulfonierten Liganden.In addition, sulfonation of the ligand in most cases significantly accelerates the reaction over the use of the unsulfonated ligand.
Durch Variation der verbrückenden Gruppen im Liganden lässt sich der Bisswinkel modifizieren, um die optimale Wirksamkeit des Liganden für den gewünschten Verwendungszweck zu erreichen.By varying the bridging groups in the ligand, the bite angle can be modified to achieve the optimal effectiveness of the ligand for the desired application.
Das erfindungsgemäße Verfahren soll durch die nachfolgenden Beispiele erläutert werden, ohne die Erfindung darauf zu beschränken:The process according to the invention shall be illustrated by the following examples, without limiting the invention thereto:
Beispiel 1 : 4,5-Bis-diphenylphosphanyl-9,9-dimethyl-9H-xanthen-2,7-bis(natrium- sulfonat) (L1)Example 1 4,5-Bis-diphenylphosphino-9,9-dimethyl-9H-xanthene-2,7-bis (sodium sulfonate) (L1)
Dieser Ligand wurde nach einer Vorschrift von van Leeuwen et al., Adv. Synth. Catal. 2002, 293 hergestellt.This ligand was prepared according to a protocol of van Leeuwen et al., Adv. Synth. Catal. 2002, 293.
Beispiel 2: Kupplung von Chlorbenzol mit 2,3-Dimethylanilin zu N-(2,3-Dimethylphenyl)- anilin unter L1-Pd-KatalyseExample 2: Coupling of chlorobenzene with 2,3-dimethylaniline to N- (2,3-dimethylphenyl) -aniline under L1-Pd catalysis
113 mg (1 mmol) Chlorbenzol, 121 mg (1 mmol) 2,3-Dimethylanilin, 192 mg (2 mmol) Natrium-tert-butoxid, 4.4 mg Palladium(ll)-acetat (2 Mol-%) und 16 mg L1 (2 Mol-%) wurden in 6 ml entgastem, wasserfreien Diglyme für 19 h auf 100 0C erhitzt. Nach dem Abkühlen wurde das Reaktionsgemisch auf 10 ml Wasser gegeben und das Gemisch mit 10 ml Toluol extrahiert. Die Toluolphase wurde zur Entfernung von Diglyme-Resten
mit 5 ml Wasser gewaschen und am Rotationsverdampfer eingeengt. Nach Trocknung im Vakuum erhielt man 188 mg (0.95 mmol, 95%) des Produkts.113 mg (1 mmol) of chlorobenzene, 121 mg (1 mmol) of 2,3-dimethylaniline, 192 mg (2 mmol) of sodium tert-butoxide, 4.4 mg of palladium (II) acetate (2 mol%) and 16 mg of L1 (2 mol%) were heated in 19 ml of degassed, anhydrous diglyme at 100 0 C for 19 h. After cooling, the reaction mixture was added to 10 ml of water, and the mixture was extracted with 10 ml of toluene. The toluene phase was used to remove diglyme residues washed with 5 ml of water and concentrated on a rotary evaporator. After drying in vacuo, 188 mg (0.95 mmol, 95%) of the product were obtained.
Beispiel 3: Kupplung von Chlorbenzol mit 2,3-Dimethylanilin zu N-(2,3-Dimethylphenyl)- anilin unter Xantphos-Pd-KatalyseExample 3: Coupling of chlorobenzene with 2,3-dimethylaniline to N- (2,3-dimethylphenyl) -aniline under Xantphos-Pd catalysis
Ausführung wie Beispiel 10, anstelle von L1 wurde zu Vergleichszwecken der käufliche Ligand Xantphos (4,5-Bis-diphenylphosphanyl-9,9-dimethyl-9H-xanthen) eingesetzt, der dem unsulfonierten L1 entspricht. Das Produkt wurde durch Flashchromatographie (Laufmittel Cyclohexan/Ethylacetat 10:1) gereinigt. Man erhielt nur 162 mg (0.82 mmol, 82 %) des Produkts.Same as Example 10, instead of L1, the commercially available ligand xantphos (4,5-bis-diphenylphosphino-9,9-dimethyl-9H-xanthene), which corresponds to the unsulfonated L1, was used for comparison. The product was purified by flash chromatography (eluent cyclohexane / ethyl acetate 10: 1). Only 162 mg (0.82 mmol, 82%) of the product were obtained.
Beispiel 4: Kupplung von 4-Chloranisol mit 2,3-Dimethylanilin zu (2,3-Dimethylphenyl)- (4-methoxyphenyl)amin unter L1-Pd-KatalyseExample 4: Coupling of 4-chloroanisole with 2,3-dimethylaniline to (2,3-dimethylphenyl) - (4-methoxyphenyl) amine under L1-Pd catalysis
143 mg (1 mmol) 4-Chloranisol, 121 mg (1 mmol) 2,3-Dimethylanilin, 192 mg (2 mmol) Natrium-tert-butoxid, 4,4 mg Palladium(ll)-acetat (2 Mol-%) und 16 mg L1 (2 Mol-%) wurden in 6 ml entgastem, wasserfreien Diglyme für 30 h auf 100 0C erhitzt. Nach dem Abkühlen wurde das Reaktionsgemisch auf 10 ml Wasser gegeben und das Gemisch mit 10 ml Toluol extrahiert. Die Toluolphase wurde zur Entfernung von Diglyme-Resten mit 5 ml Wasser gewaschen und am Rotationsverdampfer eingeengt. Nach Trocknung im Vakuum erhielt man 166 mg (0.73 mmol, 73%) des Produkts.143 mg (1 mmol) 4-chloroanisole, 121 mg (1 mmol) 2,3-dimethylaniline, 192 mg (2 mmol) sodium tert-butoxide, 4.4 mg palladium (II) acetate (2 mol%) and 16 mg of L1 (2 mol%) were heated to 100 ° C. in 6 ml of degassed, anhydrous diglyme for 30 h. After cooling, the reaction mixture was added to 10 ml of water, and the mixture was extracted with 10 ml of toluene. The toluene phase was washed with 5 ml of water to remove diglyme residues and concentrated on a rotary evaporator. After drying in vacuo, 166 mg (0.73 mmol, 73%) of the product were obtained.
Beispiel 5: Kupplung von 2-Brom-4-fluortoluol mit 2,3-Dimethylanilin zu 5-Fluor-2,2',3'- trimethyl-diphenylamin unter L1-Pd-KatalyseExample 5: Coupling of 2-bromo-4-fluorotoluene with 2,3-dimethylaniline to 5-fluoro-2,2 ', 3'-trimethyl-diphenylamine under L1-Pd catalysis
189 mg (1 mmol) 2-Brom-4-fluortoluol, 121 mg (1 mmol) 2,3-Dimethylanilin, 192 mg (2 mmol) Natrium-tert-butoxid, 4.4 mg Palladium(ll)-acetat (2 Mol-%) und 16 mg L1 (2 Mol-%) wurden in 6 ml entgastem, wasserfreien Diglyme für 15 h auf 120 0C erhitzt. Nach dem Abkühlen wurde das Reaktionsgemisch auf 10 ml Wasser gegeben und das Gemisch mit 10 ml Toluol extrahiert. Die Toluolphase wurde zur Entfernung von
Diglyme-Resten mit 5 ml Wasser gewaschen und am Rotationsverdampfer eingeengt. Nach Trocknung im Vakuum erhielt man 225 mg (0.98 mmol, 98%) des Produkts.189 mg (1 mmol) of 2-bromo-4-fluorotoluene, 121 mg (1 mmol) of 2,3-dimethylaniline, 192 mg (2 mmol) of sodium tert-butoxide, 4.4 mg of palladium (II) acetate (2 molar %) and 16 mg of L1 (2 mol%) were heated to 120 ° C. in 6 ml of degassed, anhydrous diglyme for 15 h. After cooling, the reaction mixture was added to 10 ml of water, and the mixture was extracted with 10 ml of toluene. The toluene phase was used to remove Diglyme residues washed with 5 ml of water and concentrated on a rotary evaporator. After drying in vacuo, 225 mg (0.98 mmol, 98%) of the product were obtained.
Beispiel 6: Kupplung von 1-Bromnaphtalin mit 2,3-Dimethylanilin zu (2,3- Dimethylphenyl)-naphtalin-1-ylamin unter L1-Pd-KatalyseExample 6: Coupling of 1-bromonaphthalene with 2,3-dimethylaniline to (2,3-dimethylphenyl) -naphthalen-1-ylamine under L1-Pd catalysis
Der Versuch wurde wie zuvor beschrieben durchgeführt, allerdings wurden anstelle von 2-Brom-4-fluortoluol 207 mg 1-Bromnaphtalin (1 mmol) eingesetzt. Die Ausbeute betrug 245 mg (0.99 mmol, 99%).The experiment was carried out as previously described, but 207 mg of 1-bromonaphthalene (1 mmol) were used instead of 2-bromo-4-fluorotoluene. The yield was 245 mg (0.99 mmol, 99%).
Beispiel 7: Kupplung von 4-Chloranisol mit 4-Tolylboronsäure zu 4-Methoxy-4'- methylbiphenyl unter L1-Pd-KatalyseExample 7: Coupling of 4-chloroanisole with 4-tolylboronic acid to 4-methoxy-4'-methylbiphenyl under L1-Pd catalysis
143 mg 4-Chloranisol (1 mmol), 136 mg 4-Tolylboronsäure, 0.18 mg Palladiumchlorid (0.1 Mol-%), 0.78 mg L1 (0.1 Mol-%) und 74 mg Natriumcarbonat (0.8 mmol) wurden in 1 ml Ethylenglycol und 0.2 ml Wasser suspendiert. Man erhitzte für 3 h auf 110 0C, verdünnte das Reaktionsgemisch mit 2 ml Toluol, trennte die wässrige Phase ab, extrahierte nochmals mit 2 ml Toluol und engte die vereinigten Toluolphasen am Rotationsverdampfer ein. Man erhielt 190 mg (0.96 mmol, 96%) eines farblosen Feststoffs.143 mg of 4-chloroanisole (1 mmol), 136 mg of 4-tolylboronic acid, 0.18 mg of palladium chloride (0.1 mol%), 0.78 mg of L1 (0.1 mol%) and 74 mg of sodium carbonate (0.8 mmol) were dissolved in 1 ml of ethylene glycol and 0.2 ml of water suspended. The mixture was heated for 3 h at 110 0 C, the reaction mixture was diluted with 2 ml of toluene, the aqueous phase separated, extracted again with 2 ml of toluene and concentrated the combined toluene phases on a rotary evaporator. 190 mg (0.96 mmol, 96%) of a colorless solid were obtained.
Beispiel 8: Kupplung von 2-Chlorbenzonitril mit 4-Tolylboronsäure zu 2-Cyano-4'- methylbiphenyl unter L1-Pd-KatalyseExample 8: Coupling of 2-chlorobenzonitrile with 4-tolylboronic acid to 2-cyano-4'-methylbiphenyl under L1-Pd catalysis
138 mg 2-Chlorbenzonitril (1 mmol), 136 mg 4-Tolylboronsäure, 0.18 mg Palladiumchlorid (0.1 Mol-%), 0.78 mg L1 (0.1 Mol-%) und 74 mg Natriumcarbonat (0.8 mmol) wurden in 1 ml Ethylenglycol und 0.2 ml Wasser suspendiert. Man erhitzte für 0.5 h auf 110 0C, verdünnte das Reaktionsgemisch mit 2 ml Toluol, trennte die wässrige Phase ab, extrahierte nochmals mit 2 ml Toluol und engte die vereinigten Toluolphasen am Rotationsverdampfer ein. Man erhielt 191 mg (0.99 mmol, 99%) eines farblosen Feststoffs.
Beispiel 9: Kupplung von 2-Chlorbenzonitril mit Tributylphenylstannan zu 2- Chlorbiphenyl unter L1-Pd-Katalyse138 mg of 2-chlorobenzonitrile (1 mmol), 136 mg of 4-tolylboronic acid, 0.18 mg of palladium chloride (0.1 mol%), 0.78 mg of L1 (0.1 mol%) and 74 mg of sodium carbonate (0.8 mmol) were dissolved in 1 ml of ethylene glycol and 0.2 ml of water suspended. The mixture was heated for 0.5 h at 110 0 C, the reaction mixture was diluted with 2 ml of toluene, the aqueous phase separated, extracted again with 2 ml of toluene and concentrated the combined toluene phases on a rotary evaporator. This gave 191 mg (0.99 mmol, 99%) of a colorless solid. Example 9: Coupling of 2-chlorobenzonitrile with tributylphenylstannane to 2-chlorobiphenyl under L1-Pd catalysis
138 mg 2-Chlorbenzonitril (1 mmol), 0.18 mg Palladiumchlorid (0.1 Mol-%), 0.78 mg L1 (0.1 Mol-%) und 551 mg Tributylphenylstannan (1.5 mmol) wurden in 6 ml trockenem Tetrahydrofuran gelöst und 12 h bei 60 0C gerührt. Nach dem Abkühlen versetzte man mit 305 mg DBU1 ließ 5 min rühren und extrahierte dann zweimal mit je 5 ml Wasser. Die organische Phase wurde eingeengt und durch Flash-Chromatographie (Ethylacetat/Cyclohexan 1 :9) von zinnhaltigen Rückständen befreit. Man erhielt 168 mg (0.89 mmol, 89%) eines gelblichen Feststoffs.138 mg 2-chlorobenzonitrile (1 mmol), 0.18 mg palladium chloride (0.1 mol%), 0.78 mg L1 (0.1 mol%) and 551 mg Tributylphenylstannan (1.5 mmol) were dissolved in 6 ml of dry tetrahydrofuran and 12 h at 60 0 C stirred. After cooling, it was mixed with 305 mg DBU 1 was stirred for 5 min and then extracted twice with 5 ml of water. The organic phase was concentrated and freed from tin-containing residues by flash chromatography (ethyl acetate / cyclohexane 1: 9). 168 mg (0.89 mmol, 89%) of a yellowish solid were obtained.
Beispiel 10: Kupplung von 2-Tolylmagnesiumchlorid mit 4-Chlorbenzotrifluorid unter L1- Ni-KatalyseExample 10: Coupling of 2-tolylmagnesium chloride with 4-chlorobenzotrifluoride under L1-Ni catalysis
271 mg 4-Chlorbenzotrifluorid (1.5 mmol), 0.26 mg wasserfreies Nickel(ll)-chlorid (0.02 mmol) und 1.57 mg L1 (0.02 mmol) wurden in 2 ml Tetrahydrofuran vorgelegt und 30 min auf 60 0C erwärmt. Über 2 h wurde bei dieser Temperatur 1 ml einer 1 M Lösungen von 2-Tolylmagnesiumchlorid in Tetrahydrofuran zudosiert. Man ließ noch 30 min bei dieser Temperatur nachrühren, kühlte auf Raumtemperatur ab, gab 2 ml 2 M Salzsäure zu, trennte die Phasen, wusch mit 1 ml Wasser und engte die organische Phase am Rotationsverdampfer ein. Man erhielt 215 mg (0.91 mmol, 91%) eines farblosen Öls.271 mg of 4-chlorobenzotrifluoride (1.5 mmol), 0.26 mg of anhydrous nickel (II) chloride (0.02 mmol) and 1.57 mg of L1 (0.02 mmol) were placed in 2 ml of tetrahydrofuran and heated to 60 0 C for 30 min. 1 ml of a 1 M solution of 2-tolylmagnesium chloride in tetrahydrofuran was metered in at this temperature for 2 hours. The mixture was stirred for a further 30 min at this temperature, cooled to room temperature, 2 ml of 2 M hydrochloric acid, the phases were separated, washed with 1 ml of water and the organic phase was concentrated on a rotary evaporator. This gave 215 mg (0.91 mmol, 91%) of a colorless oil.
Beispiel 11 : Kupplung von 4-Chloranisol mit Diphenylzink zu 4-Methoxybiphenyl unter L1-Pd-KatalyseExample 11 Coupling of 4-chloroanisole with diphenylzinc to 4-methoxybiphenyl under L1-Pd catalysis
143 mg 4-Chloranisol (1 mmol), 0.18 mg Palladiumchlorid (0.1 Mol-%), 0.78 mg L1 (0.1 Mol-%) und 220 mg Diphenylzink (1 mmol) wurden in 5 ml Tetrahydrofuran für 15 h auf 60 0C erhitzt. Nach dem Abkühlen auf Raumtemperatur wurden 3 ml 2 M Salzsäure zugegeben, die Phasen getrennt, mit 1 ml Wasser gewaschen und die organische
Phase am Rotationsverdampfer eingeengt. Man erhielt 171 mg (0.93 mmol, 93%) eines farblosen Feststoffs.143 mg of 4-chloroanisole (1 mmol), 0.18 mg of palladium chloride (0.1 mol%), 0.78 mg of L1 (0.1 mol%) and 220 mg of diphenylzinc (1 mmol) were heated to 60 ° C. in 5 ml of tetrahydrofuran for 15 h , After cooling to room temperature, 3 ml of 2 M hydrochloric acid were added, the phases were separated, washed with 1 ml of water and the organic Phase concentrated on a rotary evaporator. 171 mg (0.93 mmol, 93%) of a colorless solid were obtained.
Beispiel 12: Kupplung von 4-Chlorbenzophenon mit Butylacrylat zu 3-(4-Benzoyl- phenyl)-acrylsäurebutylester unter L1-Pd-KatalyseExample 12: Coupling of 4-chlorobenzophenone with butyl acrylate to 3- (4-benzoyl-phenyl) -acrylic acid butyl ester under L1-Pd catalysis
217 mg 4-Chlorbenzophenon (1 mmol), 192 mg Butylacrylat (1.5 mmol), 0.18 mg Palladiumchlorid (0.1 Mol-%) und 0.78 mg L1 (0.1 Mol-%) wurden in einem Gemisch aus 4.5 ml N.N-Dimethylacetamid und 0.5 ml Triethylamin im geschlossenen Schlenk- Gefäß 4 h auf 135 0C erhitzt. Nach dem Abkühlen wurde das Reaktionsgemisch mit 5 ml Wasser verdünnt und zweimal mit je 5 ml Toluol extrahiert. Die vereinigten Toluol- Extrakte wurden mit 3 ml Wasser gewaschen und am Rotationsverdampfer eingeengt. Man erhielt 268 mg (0.87 mmol, 87%) eines leicht gelblichen Öls.217 mg of 4-chlorobenzophenone (1 mmol), 192 mg of butyl acrylate (1.5 mmol), 0.18 mg of palladium chloride (0.1 mol%) and 0.78 mg of L1 (0.1 mol%) were dissolved in a mixture of 4.5 ml of N, N-dimethylacetamide and 0.5 ml Triethylamine in a closed Schlenk vessel heated to 135 0 C for 4 h. After cooling, the reaction mixture was diluted with 5 ml of water and extracted twice with 5 ml of toluene. The combined toluene extracts were washed with 3 ml of water and concentrated on a rotary evaporator. This gave 268 mg (0.87 mmol, 87%) of a slightly yellowish oil.
Beispiel 13: Kupplung von 4-Chlorbenzylalkohol mit Styrol zu 4-Hydroxymethylstilben unter L1-Pd-KatalyseExample 13: Coupling of 4-chlorobenzyl alcohol with styrene to 4-hydroxymethylstilbene under L1-Pd catalysis
143 mg 4-Chlorbenzophenon (1 mmol), 156 mg Styrol (1.5 mmol), 0.18 mg Palladiumchlorid (0.1 Mol-%) und 0.78 mg L1 (0.1 Mol-%) wurden in einem Gemisch aus 4.5 ml N,N-Dimethylacetamid und 0.5 ml Triethylamin im geschlossenen Schlenk- Gefäß 18 h auf 135 0C erhitzt. Nach dem Abkühlen wurde das Reaktionsgemisch mit 5 ml Wasser verdünnt und zweimal mit je 5 ml Toluol extrahiert. Die vereinigten Toluol- Extrakte wurden mit 3 ml Wasser gewaschen und am Rotationsverdampfer eingeengt. Man erhielt 189 mg (0.90 mmol, 90%) eines gelblichen Öls.143 mg of 4-chlorobenzophenone (1 mmol), 156 mg of styrene (1.5 mmol), 0.18 mg of palladium chloride (0.1 mol%) and 0.78 mg of L1 (0.1 mol%) were dissolved in a mixture of 4.5 ml of N, N-dimethylacetamide and 0.5 ml of triethylamine in a closed Schlenk vessel heated to 135 0 C for 18 h. After cooling, the reaction mixture was diluted with 5 ml of water and extracted twice with 5 ml of toluene. The combined toluene extracts were washed with 3 ml of water and concentrated on a rotary evaporator. This gave 189 mg (0.90 mmol, 90%) of a yellowish oil.
Beispiel 14: Kupplung von 4-Chloracetophenon mit Phenylacetylen zu 1-(4- Phenylethinylphenyl)-ethanon unter Katalyse durch LI-PdExample 14: Coupling of 4-chloroacetophenone with phenylacetylene to 1- (4-phenylethynylphenyl) -ethanone catalyzed by LI-Pd
155 mg 4-Chloracetophenon (1 mmol), 153 mg Phenylacetylen (1.5 mmol), 3.5 mg Palladium(ll)-chlorid (2 Mol-%), 16 mg L1 (2 Mol-%), 190 mg Kupfer(l)-iodid (1 mmol) und 212 mg Natriumcarbonat (2 mmol) wurden in 5 ml entgastem Toluol für 6 h auf
100 0C erhitzt. Nach dem Abkühlen auf Raumtemperatur wurde zweimal mit je 5 ml Wasser extrahiert und die organische Phase am Rotationsverdampfer eingeengt. Man erhielt 216 mg (0.98 mmol, 98%) eines farblosen Öls.155 mg 4-chloroacetophenone (1 mmol), 153 mg phenylacetylene (1.5 mmol), 3.5 mg palladium (II) chloride (2 mol%), 16 mg L1 (2 mol%), 190 mg copper (I) - iodide (1 mmol) and 212 mg of sodium carbonate (2 mmol) were dissolved in 5 ml of degassed toluene for 6 h 100 0 C heated. After cooling to room temperature was extracted twice with 5 ml of water and the organic phase was concentrated on a rotary evaporator. 216 mg (0.98 mmol, 98%) of a colorless oil were obtained.
Beispiel 15: Kupplung von 4-Chloranisol mit Phenylacetylen zu 1 -Methoxy-4- phenylethinylbenzol unter Katalyse durch LI-PdExample 15 Coupling of 4-chloroanisole with phenylacetylene to 1-methoxy-4-phenylethynylbenzene catalyzed by LI-Pd
143 mg 4-Chloranisol (1 mmol), 153 mg Phenylacetylen (1.5 mmol), 3.5 mg Palladium(ll)-chlorid (2 Mol-%), 16 mg L1 (2 Mol-%), 190 mg Kupfer(l)-iodid (1 mmol) und 212 mg Natriumcarbonat (2 mmol) wurden in 5 ml entgastem Toluol für 18 h auf 100 0C erhitzt. Nach dem Abkühlen auf Raumtemperatur wurde zweimal mit je 5 ml Wasser extrahiert und die organische Phase am Rotationsverdampfer eingeengt. Man erhielt 165 mg (0.79 mmol, 79%) eines farblosen Öls.143 mg 4-chloroanisole (1 mmol), 153 mg phenylacetylene (1.5 mmol), 3.5 mg palladium (II) chloride (2 mol%), 16 mg L1 (2 mol%), 190 mg copper (I) - iodide (1 mmol) and 212 mg of sodium carbonate (2 mmol) were heated in 5 ml of degassed toluene for 18 h at 100 0 C. After cooling to room temperature was extracted twice with 5 ml of water and the organic phase was concentrated on a rotary evaporator. 165 mg (0.79 mmol, 79%) of a colorless oil were obtained.
Beispiel 16: Kupplung von 4-Brombenzonitril mit Acetophenon zu 4-(2-Oxo-2- phenylethyl)-benzonitril unter L1-Pd-KatalyseExample 16: Coupling of 4-bromobenzonitrile with acetophenone to 4- (2-oxo-2-phenylethyl) benzonitrile under L1-Pd catalysis
182 mg 4-Brombenzonitril (1 mmol) und 120 mg Acetophenon (1 mmol) wurden unter Schutzgas in 5 ml N,N-Dimethylformamid gelöst und mit 192 mg Natrium-tert-butylat (2 mmol) versetzt. Man ließ 15 min rühren und gab dann 4.4 mg Palladium(ll)-acetat (2 Mol-%) und 16 mg L1 (2 Mol-%) zu und erhitzte für 8 h auf 80 °C. Zur Aufarbeitung wurden 5 ml Wasser und 10 ml Toluol zugesetzt, geschüttelt, die untere Wasserphase abgelassen und zur Entfernung restlichen Dimethylformamids nochmals mit 5 ml Wasser gewaschen. Das Lösungsmittel wurde am Rotationsverdampfer im Vakuum entfernt. Man erhielt 208 mg des Produkts (0.94 mmol, 94%).
Beispiel 17: Kupplung von 4-Brombenzonitril mit Cyclohexanon zu 4-(2-Oxocyclohexyl)- benzonitril182 mg of 4-bromobenzonitrile (1 mmol) and 120 mg of acetophenone (1 mmol) were dissolved under inert gas in 5 ml of N, N-dimethylformamide and treated with 192 mg of sodium tert-butylate (2 mmol). The mixture was stirred for 15 minutes and then 4.4 mg of palladium (II) acetate (2 mol%) and 16 mg of L1 (2 mol%) were added and the mixture was heated to 80 ° C. for 8 h. For workup, 5 ml of water and 10 ml of toluene were added, shaken, drained the lower water phase and washed to remove residual dimethylformamide again with 5 ml of water. The solvent was removed on a rotary evaporator in vacuo. 208 mg of product (0.94 mmol, 94%) were obtained. Example 17 Coupling of 4-bromobenzonitrile with cyclohexanone to 4- (2-oxocyclohexyl) benzonitrile
182 mg 4-Brombenzonitril (1 mmol) und 98 mg Cyclohexanon (1 mmol) wurden unter Schutzgas in 5 ml N,N-Dimethylformamid gelöst und mit 192 mg Natrium-tert-butylat (2 mmol) versetzt. Man ließ 15 min rühren und gab dann 4.4 mg Palladium(ll)-acetat (2 Mol-%) und 16 mg L1 (2 Mol-%) zu und erhitzte für 13 h auf 80 0C. Zur Aufarbeitung wurden 5 ml Wasser und 10 ml Toluol zugesetzt, geschüttelt, die untere Wasserphase abgelassen und zur Entfernung restlichen Dimethylformamids nochmals mit 5 ml Wasser gewaschen. Das Lösungsmittel wurde am Rotationsverdampfer im Vakuum entfernt. Man erhielt nach Flash-Chromatographie (Cyclohexan/Ethylacetat 10:1) 142 mg des Produkts (0.71 mmol, 71%).182 mg of 4-bromobenzonitrile (1 mmol) and 98 mg of cyclohexanone (1 mmol) were dissolved in 5 ml of N, N-dimethylformamide under protective gas and treated with 192 mg of sodium tert-butylate (2 mmol). The mixture was stirred for 15 minutes and then 4.4 mg of palladium (II) acetate (2 mol%) and 16 mg of L1 (2 mol%) were added and heated for 13 h at 80 0 C for work-up 5 ml of water and Added to 10 ml of toluene, shaken, drained the lower water phase and washed to remove residual dimethylformamide again with 5 ml of water. The solvent was removed on a rotary evaporator in vacuo. After flash chromatography (cyclohexane / ethyl acetate 10: 1) 142 mg of the product (0.71 mmol, 71%) were obtained.
Beispiel 18: Kupplung von 4-Chlorbrombenzol mit Malodinitril zu 1-Chlor-4- dicyanomethylbenzolExample 18: Coupling of 4-chlorobromobenzene with malodinitrile to 1-chloro-4-dicyanomethylbenzene
191 ,5 mg 4-Chlorbrombenzol (1 mmol) und 66 mg Malononitril (1 mmol) wurden unter Schutzgas in 5 ml N,N-Dimethylformamid gelöst, mit 343 mg Bariumhydroxid (2 mmol) versetzt und 1 h gerührt. Dann wurden 4.4 mg Palladium(ll)-acetat (2 Mol-%) und 16 mg L1 (2 Mol-%) zugesetzt und für 18 h auf 800C erhitzt.191.5 mg of 4-chlorobromobenzene (1 mmol) and 66 mg of malononitrile (1 mmol) were dissolved under inert gas in 5 ml of N, N-dimethylformamide, mixed with 343 mg of barium hydroxide (2 mmol) and stirred for 1 h. Then 4.4 mg of palladium (II) acetate (2 mol%) and 16 mg of L1 (2 mol%) were added and heated at 80 ° C. for 18 h.
Zur Aufarbeitung wurden 5 ml Wasser und 10 ml Toluol zugesetzt, geschüttelt, die untere Wasserphase abgelassen und zur Entfernung restlichen Dimethylformamids nochmals mit 5 ml Wasser gewaschen. Nach Entfernung des Toluols am Rotationsverdampfer erhielt man 156 mg (0.89 mmol, 89%) des Produkts.For workup, 5 ml of water and 10 ml of toluene were added, shaken, drained the lower water phase and washed to remove residual dimethylformamide again with 5 ml of water. Removal of the toluene on a rotary evaporator gave 156 mg (0.89 mmol, 89%) of the product.
Beispiel 19: Kupplung von 4-Chloracetophenon mit Zinkcyanid zu 4-Cyanoacetophenon unter L1-Pd-KatalyseExample 19: Coupling of 4-chloroacetophenone with zinc cyanide to 4-cyanoacetophenone under L1-Pd catalysis
155 mg 4-Chloracetophenon (1 mmol), 70 mg Zinkcyanid (0.6 mmol), 4,4 mg Palladium(ll)-acetat (2 Mol-%) und 16 mg L1 (2 Mol-%) wurden in 5 ml entgastem N,N-Dimethylformamid für 12 h auf 80 0C erhitzt. Nach Abkühlung auf Raumtemperatur wurde das Reaktionsgemisch mit 5 ml Wasser verdünnt und zweimal mit je 5 ml Toluol
extrahiert. Die vereinigten Toluol-Extrakte wurden nochmals mit 5 ml Wasser gewaschen und dann am Rotationsverdampfer eingeengt. Man erhielt 139 mg (0,96 mmol, 96 %) eines farblosen Feststoffs.155 mg of 4-chloroacetophenone (1 mmol), 70 mg of zinc cyanide (0.6 mmol), 4.4 mg of palladium (II) acetate (2 mol%) and 16 mg of L1 (2 mol%) were dissolved in 5 ml of degassed N , N-dimethylformamide for 12 h at 80 0 C heated. After cooling to room temperature, the reaction mixture was diluted with 5 ml of water and washed twice with 5 ml of toluene extracted. The combined toluene extracts were washed again with 5 ml of water and then concentrated on a rotary evaporator. This gave 139 mg (0.96 mmol, 96%) of a colorless solid.
Beispiel 20: Kupplung von 4-Chloranisol mit Zinkcyanid zu 4-Methoxybenzonitril unter L1-Pd-KatalyseExample 20: Coupling of 4-chloroanisole with zinc cyanide to 4-methoxybenzonitrile under L1-Pd catalysis
143 mg 4-Chloranisol (1 mmol), 70 mg Zinkcyanid (0.6 mmol), 4.4 mg Palladium(ll)- acetat (2 Mol-%) und 16 mg L1 (2 Mol-%) wurden in 5 ml entgastem143 mg of 4-chloroanisole (1 mmol), 70 mg of zinc cyanide (0.6 mmol), 4.4 mg of palladium (II) acetate (2 mol%) and 16 mg of L1 (2 mol%) were degassed in 5 ml
N,N-Dimethylformamid für 12 h auf 80 0C erhitzt. Nach Abkühlung auf Raumtemperatur wurde das Reaktionsgemisch mit 5 ml Wasser verdünnt und zweimal mit je 5 ml Toluol extrahiert. Die vereinigten Toluol-Extrakte wurden nochmals mit 5 ml Wasser gewaschen und dann am Rotationsverdampfer eingeengt. Man erhielt 117 mg (0,88 mmol, 88 %) eines farblosen Feststoffs.
N, N-dimethylformamide for 12 h at 80 0 C heated. After cooling to room temperature, the reaction mixture was diluted with 5 ml of water and extracted twice with 5 ml of toluene. The combined toluene extracts were washed again with 5 ml of water and then concentrated on a rotary evaporator. 117 mg (0.88 mmol, 88%) of a colorless solid were obtained.
Claims
1. Sulfonierte Phosphanliganden der Struktur1. Sulfonated phosphine ligands of the structure
wobei X4-7 für Kohlenstoff, Stickstoff oder Phosphor, Xi-3 und X8-io unabhängig voneinander entweder für Kohlenstoff, oder die Gruppe XjRj mit i = 2, 3, 4 oder 5 für Stickstoff oder Phosphor oder jeweils zwei benachbarte über eine formale Doppelbindung verbundene XjRj stehen gemeinsam für O, S1 NH oder NRJ;where X 4-7 is carbon, nitrogen or phosphorus, Xi -3 and X 8 -o independently of one another for carbon, or the group XjRj where i = 2, 3, 4 or 5 for nitrogen or phosphorus or two adjacent ones over one formal double bond linked XjRj together represent O, S 1 NH or NRJ;
die Reste Ri_6 stehen für Substituenten aus der Gruppe {Wasserstoff, Methyl, primäre, sekundäre oder tertiäre, cyclische oder acyclische Alkylreste mit 2 bis 20 C-Atomen, bei denen gegebenenfalls ein oder mehrere Wasserstoffatome durch Fluor oder Chlor oder Brom ersetzt sind, Hydroxy, Alkoxy, Amino, Alkylamino, Dialkylamino, Arylamino, Diarylamino, Alkylarylamino, Pentafluorsulfuranyl, Phenyl, substituiertes Phenyl, Heteroaryl, substituiertes Heteroaryl, Thio, Alkylthio, Arylthio, Diarylphosphino, Dialkylphosphino, Alkylarylphosphino, gegebenenfalls substituiertes Aminocarbonyl, CO2 ", Alkyl- oder Aryloxycarbonyl, Hydroxyalkyl, Alkoxyalkyl, Nitro, Cyano, Aryl- oder Alkylsulfon, Aryl- oder Alkylsulfonyl}, oder jeweils zwei benachbarte Reste Ri-5 stehen zusammen für einem aromatischen, heteroaromatischen oder aliphatischen ankondensierten Ring, mit der Maßgabe, dass mindestens einer der Reste Ri-3 und R4-6 einer Sulfonatgruppe entsprichtthe radicals Ri_ 6 are substituents from the group {hydrogen, methyl, primary, secondary or tertiary, cyclic or acyclic alkyl radicals having 2 to 20 C atoms, in which optionally one or more hydrogen atoms are replaced by fluorine or chlorine or bromine, hydroxy , Alkoxy, amino, alkylamino, dialkylamino, arylamino, diarylamino, alkylarylamino, pentafluorosulfuranyl, phenyl, substituted phenyl, heteroaryl, substituted heteroaryl, thio, alkylthio, arylthio, diarylphosphino, dialkylphosphino, alkylarylphosphino, optionally substituted aminocarbonyl, CO 2 " , alkyl or Aryloxycarbonyl, hydroxyalkyl, alkoxyalkyl, nitro, cyano, aryl or alkylsulfone, aryl or alkylsulfonyl}, or in each case two adjacent radicals Ri -5 together represent an aromatic, heteroaromatic or aliphatic fused ring, with the proviso that at least one of the radicals Ri -3 and R 4-6 corresponds to a sulfonate group
Yi und Y2 bedeuten unabhängig voneinander gleiche oder unterschiedliche verbrückende, zwei- oder dreibindige Strukturelemente aus der Gruppe {Sauerstoff, Schwefel, substituierter Stickstoff oder Phosphor, gegebenenfalls substituiertes Ci-3- Alkylen, -Vinylen, -Alkyliden oder Silaalkylen, gegebenenfalls substituiertes Arylen oder Heteroarylen, Carboxylat, Thiocarboxylat, N-substituiertes Carboxamid oder -imid, gegebenenfalls substituiertes Silan, Einfachbindung}, wobei der mittlere Ring aliphatischen, heteroaliphatischen, aromatischen oder heteroaromatischen Charakter haben kann; mit der Maßgabe, dass, wenn dass Y1 für -C(CH3)2- und R2=R5=Sulfonat steht, mindestens ein weiterer der Reste Ri-3 und R4-S nicht Wasserstoff ist oder mindestens eine der Gruppen Q1-4 nicht Phenyl istYi and Y 2 are each independently identical or different bridging, di- or trivalent structural elements from the group {oxygen, sulfur, substituted nitrogen or phosphorus, optionally substituted Ci -3 - alkylene, -vinylene, alkylidene or silaalkylene, optionally substituted arylene or Heteroarylene, carboxylate, thiocarboxylate, N-substituted carboxamide or imide, optionally substituted silane, single bond}, wherein the middle ring may have aliphatic, heteroaliphatic, aromatic or heteroaromatic character; with the proviso that when Y1 is -C (CH 3 ) 2 - and R 2 = R 5 = sulfonate, at least one other of Ri -3 and R 4-S is not hydrogen or at least one of Q 1-4 is not phenyl
Qi-4 bedeuten unabhängig voneinander gleiche oder unterschiedliche Reste aus der Gruppe {Wasserstoff, Methyl, lineares, verzweigtes oder cyclisches Alkyl, gegebenenfalls substituiert, Aryl, Heteroaryl, gegebenenfalls substituiert} oder Qi und Q2 oder Q3 und Q4 bilden zusammen einen Ring und stehen für ein verbrückendes Strukturelement aus der Gruppe {gegebenenfalls substituiertes Alkylen, verzweigtes Alkylen, cyclisches Alkylen, gegebenenfalls substituiertes Arylen oder Heteroarylen} oder unabhängig voneinander für einen oder zwei polycyclische Reste, wie z.B. Norbornyl oder Adamantyl; Qi-4 können eine oder mehrere Sulfonsäure- bzw. Sulfonatgruppen tragen.Qi -4 independently of one another denote identical or different radicals from the group {hydrogen, methyl, linear, branched or cyclic alkyl, optionally substituted, aryl, heteroaryl, optionally substituted} or Qi and Q 2 or Q 3 and Q 4 together form a ring and represent a bridging structural element from the group {optionally substituted alkylene, branched alkylene, cyclic alkylene, optionally substituted arylene or heteroarylene} or independently of one another for one or two polycyclic radicals, such as norbornyl or adamantyl; Qi -4 may carry one or more sulfonic acid or sulfonate groups.
2. Liganden nach Anspruch 1 , gekennzeichnet dadurch, dass Yi eine gegebenenfalls substituierte Alkylengruppe, Alkyliden-, Vinyliden- oder Vinylengruppe und Y2=O bedeutet und jeweils einer der Reste RrR3 und R4-RQ einer Sulfonatgruppe entspricht.2. Ligands according to claim 1, characterized in that Yi is an optionally substituted alkylene group, alkylidene, vinylidene or vinylene group and Y 2 = O and in each case one of the radicals RrR 3 and R 4 -RQ corresponds to a sulfonate group.
3. Liganden nach Anspruch 1 , gekennzeichnet dadurch, dass Yi eine gegebenenfalls substituierte Silylen- oder Silaalkylengruppe und Y2=O bedeutet und jeweils einer der Reste RrR3 und R4-Re einer Sulfonatgruppe entspricht.3. Ligands according to claim 1, characterized in that Yi is an optionally substituted silylene or silaalkylene group and Y 2 = O and in each case one of the radicals RrR 3 and R 4 -Re corresponds to a sulfonate group.
4. Liganden nach Anspruch 1 , gekennzeichnet dadurch, dass Yi ein Schwefelatom oder eine gegebenenfalls substituierte Thiaalkylengruppe und Y2=O bedeutet und jeweils einer der Reste RrR3 und R4-Re einer Sulfonatgruppe entspricht.4. Ligands according to claim 1, characterized in that Yi is a sulfur atom or an optionally substituted thiaalkylene group and Y 2 = O and in each case one of the radicals RrR 3 and R 4 -Re corresponds to a sulfonate group.
5. Liganden nach Anspruch 1 , gekennzeichnet dadurch, dass Yi eine Einfachbindung und Y2=O bedeutet und jeweils einer der Reste RrR3 und R4-R6 einer Sulfonatgruppe entspricht. 5. Ligands according to claim 1, characterized in that Yi is a single bond and Y 2 = O and in each case one of the radicals RrR 3 and R 4 -R 6 corresponds to a sulfonate group.
6. Liganden nach Anspruch 1 , gekennzeichnet dadurch, dass Y1 ein substituiertes Stickstoffatom oder eine N-substituierte Azaalkylengruppe und Y2=O bedeutet und jeweils einer der Reste R1-R3 und R4-RO einer Sulfonatgruppe entspricht.6. Ligands according to claim 1, characterized in that Y 1 represents a substituted nitrogen atom or an N-substituted azaalkylene group and Y 2 = O and in each case one of the radicals R 1 -R 3 and R 4 -RO corresponds to a sulfonate group.
7. Liganden nach Anspruch 3-6, gekennzeichnet dadurch, dass Yi anstelle von Sauerstoff Schwefel bedeutet.7. ligands according to claim 3-6, characterized in that Yi is sulfur instead of oxygen.
8. Katalysatorsysteme enthaltend mindestens einen Liganden der folgenden Formel8. Catalyst systems containing at least one ligand of the following formula
R3 R4R3 R4
I II i
Qr CL Q^ Q 4 Q r CL Q ^ Q 4
sowie mindestens ein Salz, einen Komplex oder eine metallorganische Verbindung eines Metalls der Gruppe {Mn, Fe, Co, Ni, Cu, Rh, Pd, Ir, Pt}, bevorzugt Palladium oder Nickel, und wobei die Symbole R 1-6, Xi-io, Y 1+2 und Qi-4 die in Anspruch 1 genannte Bedeutung haben.and at least one salt, complex or organometallic compound of a metal of the group {Mn, Fe, Co, Ni, Cu, Rh, Pd, Ir, Pt}, preferably palladium or nickel, and wherein the symbols R 1-6, Xi -io, Y 1 + 2 and Qi -4 have the meaning given in claim 1.
9. Verwendung eines Katalysatorsystems nach Anspruch 8 für Kreuzkupplungsreaktionen von Aryl- und Heteroarylhalogeniden und -sulfonaten mit Aminen, Alkoholen und Kohlenstoffnucleophilen.9. Use of a catalyst system according to claim 8 for cross-coupling reactions of aryl and heteroaryl halides and sulfonates with amines, alcohols and carbon nucleophiles.
10. Verfahren zur Kreuzkupplung von Aryl- und Heteroarylhalogeniden und -sulfonaten mit Aminen, Alkoholen und Kohlenstoffnucleophilen, dadurch gekennzeichnet, dass die Kreuzkupplung in Gegenwart eines Liganden gemäß mindestens einem der Ansprüche 1 bis 8, einem Übergangsmetall der Gruppe {Mn, Fe1 Co, Ni, Rh, Pd, Ir, Pt} und einer Bronsted-Base in einem Lösungsmittel oder Lösungsmittelgemisch durchgeführt wird. 10. A process for the cross-coupling of aryl and heteroaryl halides and sulfonates with amines, alcohols and carbon nucleophiles, characterized in that the cross-coupling in the presence of a ligand according to any one of claims 1 to 8, a transition metal of the group {Mn, Fe 1 Co, Ni, Rh, Pd, Ir, Pt} and a Bronsted base in a solvent or solvent mixture.
11. Verfahren nach Anspruch 10, dadurch gekennzeichnet, dass als Bronsted-Base ein Hydroxid oder Alkoholat der Alkali- oder Erdalkalimetalle oder ein Alkalicarbonat oder -phosphat oder Gemische dieser Verbindungen eingesetzt werden.11. The method according to claim 10, characterized in that as Bronsted base, a hydroxide or alkoxide of the alkali or alkaline earth metals or an alkali carbonate or phosphate or mixtures of these compounds are used.
12. Verfahren nach Anspruch 10 oder 11 , dadurch gekennzeichnet, dass 1 ,0 bis 3 Äquivalente an Base bezogen auf das Aryl- oder Heteroarylhalogenid bzw. Aryl- oder12. The method according to claim 10 or 11, characterized in that 1, 0 to 3 equivalents of base based on the aryl or heteroaryl halide or aryl or
Heteroarylsulfonat eingesetzt werden.Heteroarylsulfonate be used.
13. Verfahren nach mindestens einem der Ansprüche 10 bis 12, dadurch gekennzeichnet, dass als Lösungsmittel offenkettige und cyclische Ether und Diether, Oligo- und Polyether sowie substituierte einfache oder mehrfache Alkohole und gegebenenfalls substituierte Aromaten, N,N-Dimethylformamid, Dimethylacetamid, Dimethylsulfoxid, N-Methylpyrrolidon, tertiäre Amine, Acetonitril, Propionitril oder ein Gemisch mehrerer dieser Lösungsmittel eingesetzt wird.13. The method according to at least one of claims 10 to 12, characterized in that as the solvent open-chain and cyclic ethers and diethers, oligo- and polyethers and substituted mono- or polyhydric alcohols and optionally substituted aromatics, N, N-dimethylformamide, dimethylacetamide, dimethyl sulfoxide, N-methylpyrrolidone, tertiary amines, acetonitrile, propionitrile or a mixture of several of these solvents is used.
14. Verfahren nach mindestens einem der Ansprüche 10 bis 13, dadurch gekennzeichnet, dass die Reaktion bei einer Temperatur im Bereich von -20 bis 2400C durchgeführt wird.14. The method according to at least one of claims 10 to 13, characterized in that the reaction is carried out at a temperature in the range of -20 to 240 0 C.
15. Verfahren nach Anspruch 14, dadurch gekennzeichnet, dass die Reaktion bei einer Temperatur im Bereich von 0 bis 1500C durchgeführt wird.15. The method according to claim 14, characterized in that the reaction is carried out at a temperature in the range of 0 to 150 0 C.
16. Verfahren nach mindestens einem der Ansprüche 10 bis 15, dadurch gekennzeichnet, dass als Katalysator oder Präkatalysator ein Salz, ein Komplex oder eine metallorganische Verbindung eines Metalls der Gruppe {Fe, Co, Ni, Pd} eingesetzt wird.16. The method according to at least one of claims 10 to 15, characterized in that a salt, a complex or an organometallic compound of a metal of the group {Fe, Co, Ni, Pd} is used as the catalyst or precatalyst.
17. Verfahren nach mindestens einem der Ansprüche 10 bis 16, dadurch gekennzeichnet, dass der Katalysator im Verhältnis zum Reaktanden in Mengen von 0.001 Mol-% bis 100 Mol-% eingesetzt wird. 17. The method according to at least one of claims 10 to 16, characterized in that the catalyst in relation to the reactant in amounts of 0.001 mol% to 100 mol% is used.
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PCT/EP2006/012107 WO2007071345A1 (en) | 2005-12-20 | 2006-12-15 | Sulfonated phosphine ligands and process for cross-coupling aryl halides and arylsulfonates and heteroaryl halides and heteroarylsulfonates with amines, alcohols and carbon nucleophiles by using the ligands in conjunction with transition metal catalysts |
Country Status (2)
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DE (1) | DE102005060821A1 (en) |
WO (1) | WO2007071345A1 (en) |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1995030680A1 (en) * | 1994-05-06 | 1995-11-16 | Dsm N.V. | Bidentate phosphine ligand |
EP1400504A1 (en) * | 2002-09-19 | 2004-03-24 | Celanese Chemicals Europe GmbH | Process for the preparation of aldehydes |
-
2005
- 2005-12-20 DE DE102005060821A patent/DE102005060821A1/en not_active Withdrawn
-
2006
- 2006-12-15 WO PCT/EP2006/012107 patent/WO2007071345A1/en active Application Filing
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1995030680A1 (en) * | 1994-05-06 | 1995-11-16 | Dsm N.V. | Bidentate phosphine ligand |
EP1400504A1 (en) * | 2002-09-19 | 2004-03-24 | Celanese Chemicals Europe GmbH | Process for the preparation of aldehydes |
Non-Patent Citations (1)
Title |
---|
MUL W P ET AL: "New, highly efficient work-up protocol for sulfonated diphosphines", ADVANCED SYNTHESIS & CATALYSIS, WILEY VCH VERLAG, WEINHEIM, DE, vol. 344, no. 3-4, 2002, pages 293 - 298, XP002261499, ISSN: 1615-4150 * |
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DE102005060821A1 (en) | 2007-06-28 |
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