CN114409714B - 一种合成1,3-二取代平面手性金属茂化合物的方法 - Google Patents
一种合成1,3-二取代平面手性金属茂化合物的方法 Download PDFInfo
- Publication number
- CN114409714B CN114409714B CN202210052476.4A CN202210052476A CN114409714B CN 114409714 B CN114409714 B CN 114409714B CN 202210052476 A CN202210052476 A CN 202210052476A CN 114409714 B CN114409714 B CN 114409714B
- Authority
- CN
- China
- Prior art keywords
- disubstituted
- reaction
- cdcl
- nmr
- compound
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 81
- 238000000034 method Methods 0.000 title claims abstract description 64
- 230000002194 synthesizing effect Effects 0.000 title claims abstract description 16
- 238000006243 chemical reaction Methods 0.000 claims abstract description 21
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims abstract description 20
- 239000003054 catalyst Substances 0.000 claims abstract description 11
- 239000002994 raw material Substances 0.000 claims abstract description 10
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 claims abstract description 8
- 229910052707 ruthenium Inorganic materials 0.000 claims abstract description 8
- 239000003513 alkali Substances 0.000 claims abstract description 6
- 229910052763 palladium Inorganic materials 0.000 claims abstract description 6
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 6
- 150000001413 amino acids Chemical class 0.000 claims abstract description 5
- 230000009471 action Effects 0.000 claims abstract description 4
- 239000003960 organic solvent Substances 0.000 claims abstract description 4
- 238000003756 stirring Methods 0.000 claims abstract description 4
- 125000003518 norbornenyl group Chemical class C12(C=CC(CC1)C2)* 0.000 claims abstract 3
- 239000011541 reaction mixture Substances 0.000 claims description 15
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 12
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical group [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 11
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 8
- 239000011261 inert gas Substances 0.000 claims description 6
- 125000003118 aryl group Chemical group 0.000 claims description 5
- 238000004440 column chromatography Methods 0.000 claims description 5
- -1 heterocyclic aryl Chemical group 0.000 claims description 5
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 230000015572 biosynthetic process Effects 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 150000002148 esters Chemical class 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 4
- 229910052710 silicon Inorganic materials 0.000 claims description 4
- 239000010703 silicon Substances 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 4
- SZXBQTSZISFIAO-ZETCQYMHSA-N (2s)-3-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoic acid Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)OC(C)(C)C SZXBQTSZISFIAO-ZETCQYMHSA-N 0.000 claims description 3
- 125000003342 alkenyl group Chemical group 0.000 claims description 3
- 125000000304 alkynyl group Chemical group 0.000 claims description 3
- 125000003368 amide group Chemical group 0.000 claims description 3
- 150000001502 aryl halides Chemical class 0.000 claims description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 239000001301 oxygen Substances 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
- 230000008569 process Effects 0.000 claims description 3
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 2
- 239000003570 air Substances 0.000 claims description 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 125000001246 bromo group Chemical group Br* 0.000 claims description 2
- 238000001914 filtration Methods 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 229910052740 iodine Chemical group 0.000 claims description 2
- 239000011630 iodine Chemical group 0.000 claims description 2
- 229910052742 iron Inorganic materials 0.000 claims description 2
- SUNLGPFGQCUGLS-UHFFFAOYSA-N 1-heptylbicyclo[2.2.1]hept-2-ene Chemical group C(CCCCCC)C12C=CC(CC1)C2 SUNLGPFGQCUGLS-UHFFFAOYSA-N 0.000 claims 1
- 125000004036 acetal group Chemical group 0.000 claims 1
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims 1
- 150000002431 hydrogen Chemical class 0.000 claims 1
- 238000002360 preparation method Methods 0.000 abstract description 26
- 150000001503 aryl iodides Chemical class 0.000 abstract description 21
- 150000001499 aryl bromides Chemical class 0.000 abstract description 10
- 229910052757 nitrogen Inorganic materials 0.000 abstract description 5
- 239000000758 substrate Substances 0.000 abstract description 4
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 44
- 238000004128 high performance liquid chromatography Methods 0.000 description 22
- 239000007788 liquid Substances 0.000 description 20
- 125000001424 substituent group Chemical group 0.000 description 9
- 239000012298 atmosphere Substances 0.000 description 8
- 239000007810 chemical reaction solvent Substances 0.000 description 8
- 239000012039 electrophile Substances 0.000 description 8
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 238000004252 FT/ICR mass spectrometry Methods 0.000 description 6
- 238000013313 FeNO test Methods 0.000 description 6
- KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical class [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 description 5
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical class C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical class CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000012300 argon atmosphere Substances 0.000 description 3
- 238000006555 catalytic reaction Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 150000002848 norbornenes Chemical class 0.000 description 3
- 238000001308 synthesis method Methods 0.000 description 3
- DQXKOHDUMJLXKH-PHEQNACWSA-N (e)-n-[2-[2-[[(e)-oct-2-enoyl]amino]ethyldisulfanyl]ethyl]oct-2-enamide Chemical compound CCCCC\C=C\C(=O)NCCSSCCNC(=O)\C=C\CCCCC DQXKOHDUMJLXKH-PHEQNACWSA-N 0.000 description 2
- FYGHSUNMUKGBRK-UHFFFAOYSA-N 1,2,3-trimethylbenzene Chemical class CC1=CC=CC(C)=C1C FYGHSUNMUKGBRK-UHFFFAOYSA-N 0.000 description 2
- WHQVXHBSTRFRCE-UHFFFAOYSA-N 2-fluoro-4-iodobenzonitrile Chemical compound FC1=CC(I)=CC=C1C#N WHQVXHBSTRFRCE-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical class CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 239000004215 Carbon black (E152) Substances 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 125000002777 acetyl group Chemical class [H]C([H])([H])C(*)=O 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- 150000001335 aliphatic alkanes Chemical class 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 238000007306 functionalization reaction Methods 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 125000002524 organometallic group Chemical group 0.000 description 2
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 2
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- VJFLMYRRJUWADI-UHFFFAOYSA-N (3alpha,16beta)-12-Ursene-3,16-diol Natural products C1CC(O)C(C)(C)C2CCC3(C)C4(C)CC(O)C5(C)CCC(C)C(C)C5C4=CCC3C21C VJFLMYRRJUWADI-UHFFFAOYSA-N 0.000 description 1
- VJFLMYRRJUWADI-DBHRHCOISA-N (3s,4ar,6ar,6bs,8r,8as,11r,12s,12as,14ar,14br)-4,4,6a,6b,8a,11,12,14b-octamethyl-2,3,4a,5,6,7,8,9,10,11,12,12a,14,14a-tetradecahydro-1h-picene-3,8-diol Chemical compound C1C[C@H](O)C(C)(C)[C@@H]2CC[C@@]3(C)[C@]4(C)C[C@@H](O)[C@@]5(C)CC[C@@H](C)[C@H](C)[C@H]5C4=CC[C@@H]3[C@]21C VJFLMYRRJUWADI-DBHRHCOISA-N 0.000 description 1
- DDXDGBOZDFYVGL-UHFFFAOYSA-N (4-iodophenyl) 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OC1=CC=C(I)C=C1 DDXDGBOZDFYVGL-UHFFFAOYSA-N 0.000 description 1
- SYSZENVIJHPFNL-UHFFFAOYSA-N (alpha-D-mannosyl)7-beta-D-mannosyl-diacetylchitobiosyl-L-asparagine, isoform B (protein) Chemical compound COC1=CC=C(I)C=C1 SYSZENVIJHPFNL-UHFFFAOYSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- VDFVNEFVBPFDSB-UHFFFAOYSA-N 1,3-dioxane Chemical compound C1COCOC1 VDFVNEFVBPFDSB-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- SWJPEBQEEAHIGZ-UHFFFAOYSA-N 1,4-dibromobenzene Chemical compound BrC1=CC=C(Br)C=C1 SWJPEBQEEAHIGZ-UHFFFAOYSA-N 0.000 description 1
- LFMWZTSOMGDDJU-UHFFFAOYSA-N 1,4-diiodobenzene Chemical compound IC1=CC=C(I)C=C1 LFMWZTSOMGDDJU-UHFFFAOYSA-N 0.000 description 1
- WYECURVXVYPVAT-UHFFFAOYSA-N 1-(4-bromophenyl)ethanone Chemical compound CC(=O)C1=CC=C(Br)C=C1 WYECURVXVYPVAT-UHFFFAOYSA-N 0.000 description 1
- JZJWCDQGIPQBAO-UHFFFAOYSA-N 1-(4-iodophenyl)ethanone Chemical compound CC(=O)C1=CC=C(I)C=C1 JZJWCDQGIPQBAO-UHFFFAOYSA-N 0.000 description 1
- SEAOBYFQWJFORM-UHFFFAOYSA-N 1-bromo-4-(trifluoromethoxy)benzene Chemical compound FC(F)(F)OC1=CC=C(Br)C=C1 SEAOBYFQWJFORM-UHFFFAOYSA-N 0.000 description 1
- ZDFBKZUDCQQKAC-UHFFFAOYSA-N 1-bromo-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(Br)C=C1 ZDFBKZUDCQQKAC-UHFFFAOYSA-N 0.000 description 1
- TYHUGKGZNOULKD-UHFFFAOYSA-N 1-fluoro-2-iodobenzene Chemical compound FC1=CC=CC=C1I TYHUGKGZNOULKD-UHFFFAOYSA-N 0.000 description 1
- KGNQDBQYEBMPFZ-UHFFFAOYSA-N 1-fluoro-4-iodobenzene Chemical compound FC1=CC=C(I)C=C1 KGNQDBQYEBMPFZ-UHFFFAOYSA-N 0.000 description 1
- DUVVOUSAQUQNMU-UHFFFAOYSA-N 1-iodo-4-(4-iodophenyl)sulfanylbenzene Chemical compound C1=CC(I)=CC=C1SC1=CC=C(I)C=C1 DUVVOUSAQUQNMU-UHFFFAOYSA-N 0.000 description 1
- RTUDBROGOZBBIC-UHFFFAOYSA-N 1-iodo-4-(trifluoromethoxy)benzene Chemical compound FC(F)(F)OC1=CC=C(I)C=C1 RTUDBROGOZBBIC-UHFFFAOYSA-N 0.000 description 1
- SKGRFPGOGCHDPC-UHFFFAOYSA-N 1-iodo-4-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=C(I)C=C1 SKGRFPGOGCHDPC-UHFFFAOYSA-N 0.000 description 1
- UDHAWRUAECEBHC-UHFFFAOYSA-N 1-iodo-4-methylbenzene Chemical compound CC1=CC=C(I)C=C1 UDHAWRUAECEBHC-UHFFFAOYSA-N 0.000 description 1
- SCCCFNJTCDSLCY-UHFFFAOYSA-N 1-iodo-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(I)C=C1 SCCCFNJTCDSLCY-UHFFFAOYSA-N 0.000 description 1
- NXYICUMSYKIABQ-UHFFFAOYSA-N 1-iodo-4-phenylbenzene Chemical group C1=CC(I)=CC=C1C1=CC=CC=C1 NXYICUMSYKIABQ-UHFFFAOYSA-N 0.000 description 1
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 description 1
- ZRYZBQLXDKPBDU-UHFFFAOYSA-N 4-bromobenzaldehyde Chemical compound BrC1=CC=C(C=O)C=C1 ZRYZBQLXDKPBDU-UHFFFAOYSA-N 0.000 description 1
- NIEBHDXUIJSHSL-UHFFFAOYSA-N 4-iodobenzaldehyde Chemical compound IC1=CC=C(C=O)C=C1 NIEBHDXUIJSHSL-UHFFFAOYSA-N 0.000 description 1
- XOKDXPVXJWTSRM-UHFFFAOYSA-N 4-iodobenzonitrile Chemical compound IC1=CC=C(C#N)C=C1 XOKDXPVXJWTSRM-UHFFFAOYSA-N 0.000 description 1
- 239000005489 Bromoxynil Substances 0.000 description 1
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical class CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical class CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical class CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 239000005662 Paraffin oil Substances 0.000 description 1
- 101150003085 Pdcl gene Proteins 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 1
- YCOXTKKNXUZSKD-UHFFFAOYSA-N as-o-xylenol Natural products CC1=CC=C(O)C=C1C YCOXTKKNXUZSKD-UHFFFAOYSA-N 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 244000022203 blackseeded proso millet Species 0.000 description 1
- ZOAIGCHJWKDIPJ-UHFFFAOYSA-M caesium acetate Chemical compound [Cs+].CC([O-])=O ZOAIGCHJWKDIPJ-UHFFFAOYSA-M 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
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000012069 chiral reagent Substances 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- SNHMUERNLJLMHN-UHFFFAOYSA-N iodobenzene Chemical compound IC1=CC=CC=C1 SNHMUERNLJLMHN-UHFFFAOYSA-N 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- CZNGTXVOZOWWKM-UHFFFAOYSA-N methyl 4-bromobenzoate Chemical compound COC(=O)C1=CC=C(Br)C=C1 CZNGTXVOZOWWKM-UHFFFAOYSA-N 0.000 description 1
- DYUWQWMXZHDZOR-UHFFFAOYSA-N methyl 4-iodobenzoate Chemical compound COC(=O)C1=CC=C(I)C=C1 DYUWQWMXZHDZOR-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- VYQNWZOUAUKGHI-UHFFFAOYSA-N monobenzone Chemical compound C1=CC(O)=CC=C1OCC1=CC=CC=C1 VYQNWZOUAUKGHI-UHFFFAOYSA-N 0.000 description 1
- JFNLZVQOOSMTJK-KNVOCYPGSA-N norbornene Chemical compound C1[C@@H]2CC[C@H]1C=C2 JFNLZVQOOSMTJK-KNVOCYPGSA-N 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 150000002940 palladium Chemical class 0.000 description 1
- 235000011056 potassium acetate Nutrition 0.000 description 1
- WFIZEGIEIOHZCP-UHFFFAOYSA-M potassium formate Chemical compound [K+].[O-]C=O WFIZEGIEIOHZCP-UHFFFAOYSA-M 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000002390 rotary evaporation Methods 0.000 description 1
- FZHCFNGSGGGXEH-UHFFFAOYSA-N ruthenocene Chemical compound [Ru+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 FZHCFNGSGGGXEH-UHFFFAOYSA-N 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 229920002545 silicone oil Polymers 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- IAQRGUVFOMOMEM-ONEGZZNKSA-N trans-but-2-ene Chemical group C\C=C\C IAQRGUVFOMOMEM-ONEGZZNKSA-N 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 229910000404 tripotassium phosphate Inorganic materials 0.000 description 1
- 235000019798 tripotassium phosphate Nutrition 0.000 description 1
- 239000008096 xylene Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F17/00—Metallocenes
- C07F17/02—Metallocenes of metals of Groups 8, 9 or 10 of the Periodic System
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
本发明公开了一种合成1,3‑二取代平面手性金属茂化合物的方法,属于有机合成领域。本发明方法以简单的N,N‑烷基氨基甲基二茂铁/钌和芳基碘化物或芳基溴化物为起始原料,在钯催化剂、手性氨基酸、降冰片烯衍生物以及碱的作用下,在80℃下于有机溶剂中搅拌反应,即可得到1,3‑二取代平面手性金属茂化合物。该方法所用的原料廉价易得,反应条件温和,底物普适性好,产率高,制备过程简单。
Description
技术领域
本发明涉及一种合成1,3-二取代平面手性金属茂化合物的方法,属于有机合成领域。
背景技术
二茂铁化合物在材料化学、催化和药物化学等领域中发挥着重要作用,尤其是含有平面手性的二茂铁化合物,作为手性配体或者手性催化剂被广泛应用于不对称催化反应中([1]Fu,G.C.Acc.Chem.Res.2000,33,412-420;[2]Dai,L.-X.;Tu,T.;You,S.-L.;Deng,W.-P.;Hou,X.-L.Acc.Chem.Res.2003,36,659-667;[3]Atkinson,R.C.J.;Gibson,V.C.;Long,N.J.Chem.Soc.Rev.2004,33,313-328;[4]Arrayás,R.-G.;Adrio,J.;Carretero,J.-C.Angew.Chem.Int.Ed.2006,45,7674-7715;[5]Dai,L.-X.;Hou,X.-L.Chiral Ferrocenesin Asymmetric Catalysis,Wiley,Weinheim,2010)。鉴于此类结构骨架的重要性,化学家发展了诸多合成方法,其中对于1,2-二取代的平面手性二茂铁化合物的研究较多,常见的合成策略有:(1)手性辅基导向的非对映选择性邻位锂化([1]Battelle,L.F.;Bau,R.;Gokel,G.W.;Oyakawa,R.T.;Ugi,I.K.J.Am.Chem.Soc.1973,95,482;[2]Bolm,C.;Kesselgruber,M.;K.;Raabe,G.Organometallics 2000,19,1648.);(2)使用当量的外加手性试剂的对映选择性邻位锂化([1]Tsukazaki,M.;Tinkl,M.;Roglans,A.;Chapell,B.J.;Taylor,N.J.;Snieckus,V.J.Am.Chem.Soc.1996,118,685;[2]Genet,C.;Canipa,S.J.;O’Brein,P.;Taylor,S.J.Am.Chem.Soc.2006,128,9336.);(3)去对称化策略([1]Mercier,A.;Yeo,W.C.;Chou,J.;Chaudhuri,P.D.;Bernard-inelli,G.;Kündig,E.P.Chem.Commun.2009,5227;[2]Ogasawara,M.;Watanabe,S.;Nakajima,K.;Takahashi,T.J.Am.Chem.Soc.2010,132,2136.);(4)消旋体的手性拆分([1]Alba,A.-N.;Rios,R.Molecules 2009,14,4747;Ogasawara,M.;Arae,S.;Watanabe,S.;Nakajima,K.;Takahashi,T.ACS Catal.2016,6,1308.);(5)以及过渡金属催化的不对称碳氢键官能团化反应等([1]Liu,C.-X.;Gu,Q.;You,S.-L.Trends Chem.2020,2,737;[2]Liu,C.-X.;Cai,Z.-J.;Wang,Q.;Wu,Z.-J.;Gu,Q.;You,S.-L.CCS Chem.2020,2,642;[3]Lou,S.;Zhuo,Q.;Nishiura,M.;Luo,G.;Hou,Z.J.Am.Chem.Soc.2021,143,2470.)。当前对1,3-二取代的平面手性二茂铁化合物的研究较少,合成方法十分有限,主要有:(1)消旋体的手性拆分策略([1]Westman,L.;Richard,Jr.K.L.Acta Chem.Scand.1962,16,1199;[2]Aratani,T.;Gonda,T.;Nozaki,H.Tetrahedron 1970,26,5453;[3]Chuard,T.;Cowling,S.J.;Fernandez-Ciurleo,M.;Jauslin,I.;Goodby,J.W.;Deschenaux,R.Chem.Commun.2000,2109.);(2)以及先引入可消除的第二个邻位导向基团,实现间位的官能团化,然后再将第二个邻位导向基团消除的多步转换策略([1]Ferber,B.;Top,S.;Welter,R.;Jaouen,G.Chem.Eur.J.2006,12,2081;[2]Steurer,M.;Wang,Y.;Mereiter,K.;Weissensteiner,W.Organometallics 2007,26,3850.)。然而,这些方法大多需要预先合成特殊官能团的底物,或者需要较为复杂的催化剂,极大地限制了这些方法的使用范围。因此发展高效、简洁的合成新方法显得尤为重要。本发明以易得的N,N-烷基氨基甲基二茂铁/钌和芳基卤化物为起始原料,在钯催化剂、手性氨基酸、降冰片烯衍生物和碱的作用下,在25℃到100℃下于有机溶剂中搅拌反应,即可得1,3-二取代平面手性金属茂化合物。该方法所用的原料廉价易得,反应条件温和,底物普适性好,产率高,制备过程简单。
发明内容
为了解决现有技术中存在的不足,本发明提供一种合成1,3-二取代平面手性金属茂化合物的方法。该方法所用的原料廉价易得,反应条件温和,底物普适性好,产率高,制备过程简单。
本发明提供的技术方案具体如下:
本发明的目的之一在于提供一种合成1,3-二取代平面手性金属茂化合物的方法,包括以下步骤:
以N,N-烷基氨基甲基二茂铁/钌A和芳基卤化物B为起始原料,在钯催化剂C、手性氨基酸D、降冰片烯衍生物E和碱F的作用下,于有机溶剂G中搅拌反应直至反应结束,将反应混合物后处理即得到如式I的1,3-二取代平面手性金属茂化合物,所述反应式如下:
其中:
R1,R2为烷基,两个基团可以相同也可以不同,也可以相互连接;
R3选自氢、芳基、烷基、缩醛基、硅基、或卤素;
X为溴或者碘;
M为铁或者钌;
R4选自芳基、杂环芳基、烷基、酯基、醛基、羟基、硅基、氨基、氰基、硝基、酰胺基、磺酰基、烷氧基、烯基、炔基、卤素中的一种或几种;
m表示R4的个数,0≤m≤2;当m=2时,两个基团可以相同也可以不同;
Ar1为芳烃及杂环芳烃。
上述的一种合成1,3-二取代平面手性金属茂化合物的方法,所述钯催化剂C选自Pd(PPh3)4、Pd(dba)2、Pd2(dba)3、Pd(OAc)2、Pd(PhCN)2Cl2、Pd(MeCN)2Cl2、PdCl2、PdI2、[Pd(allyl)Cl]2中的任意一种或几种。
上述的一种合成1,3-二取代平面手性金属茂化合物的方法,所述手性氨基酸D的结构式为:
其中:
i)R5选自苯甲酰基、乙酰基、苄氧羰基、叔丁氧羰基、酯基、甲基、苄基中的任意一种;
ii)R6选自芳基或烷基中的任意一种。
上述的一种合成1,3-二取代平面手性金属茂化合物的方法,所述降冰片烯衍生物E的结构式为:
其中:
i)R7为左边五元环上的取代基,n代表取代基个数,0≤n≤8;R7为双键上的取代基,p代表取代基个数,0≤p≤2;
ii)R7,R8选自芳基、杂环芳基、烷基、酯基、醛基、羧基、羟基、硅基、氨基、氰基、硝基、酰胺基、磺酰基、烷氧基、烯基、炔基或卤素中的任意一种或几种;
iii)左边五元环上取代基数目为2个及2个以上时,可以相同,也可以不相同;双键上的取代基数目为2个时,可以相同,也可以不相同;
iv)R7和R8取代基的种类可以相同,也可以不相同。
上述的一种合成1,3-二取代平面手性金属茂化合物的方法,所述碱F选自碳酸钠、碳酸钾、碳酸铯、醋酸钠、醋酸钾、醋酸铯、磷酸三钾、甲酸钾、氢氧化钠、叔丁醇钠中的任意一种或几种。
上述的一种合成1,3-二取代平面手性金属茂化合物的方法,所述溶剂G选自甲醇、乙醇、异丙醇、叔丁醇、四氢呋喃、2-甲基四氢呋喃、乙醚、二甲基乙二醚、甲基叔丁基醚、1,4-二氧六烷、1,3-二氧六烷、二氯甲烷、1,2-二氯乙烷、氯仿、四氯化碳、C4-12的饱和烷烃、C3-12的氟代或者氯代烷烃、苯、甲苯、二甲苯、三甲苯、二甲基亚砜、N,N-二甲基甲酰胺、N,N-二甲基乙酰胺、丙酮、N-甲基吡咯烷酮、乙腈、C3-12的饱和烷基腈中的任意一种或几种。
上述的一种合成1,3-二取代平面手性金属茂化合物的方法,反应在空气、氧气或惰性气体保护下进行。
上述的一种合成1,3-二取代平面手性金属茂化合物的方法,反应在惰性气体保护下进行。惰性气体的效果优于空气和氧气,而惰性气体中尤以氩气的效果最佳。
上述的一种合成1,3-二取代平面手性金属茂化合物的方法,所述后处理方法为:将反应混合物过滤、浓缩、柱层析纯化即得到如式I的1,3-二取代平面手性金属茂化合物。
本发明的目的之二在于提供利用上述方法制备的1,3-二取代平面手性金属茂化合物。
本发明所述的合成1,3-二取代平面手性金属茂化合物的方法中,反应时间为1~48小时,反应温度为25℃~100℃。加热过程可采用油浴(如硅油、石蜡油等)或者其它加热方式。
本发明优选在反应完成后对反应产物进行后处理,包括萃取、浓缩和纯化。所述萃取过程可使用分液漏斗进行萃取。所述浓缩过程可采用减压蒸馏等方法,例如用旋转蒸发仪减压浓缩。所述纯化方法可采用柱层析分离纯化。
本发明的方法可以高效地制备1,3-二取代平面手性金属茂化合物,具有以下有益效果:
1、本发明所涉及的主要原料N,N-烷基氨基甲基二茂铁/钌为商业化原料(其衍生物仅需用简单的商业化原料二茂铁/钌经过一到两步快速合成);另一原料芳基碘代物、芳基溴化物均为商品化试剂,无需特殊处理,且价格低廉,种类繁多;
2、本发明方法具有非常好的对映选择性,所得产物的ee值高达99%;
3、本发明方法所涉及的反应使用的催化剂是较为廉价的金属钯盐,相比于其他合成方法所使用的当量的有机金属试剂是一个重要的改进及补充;
4、本发明方法所涉及的反应使用的催化量的降冰片烯衍生物,相比于之前的反应使用的降冰片烯的用量大大减少;
5、本发明方法所涉及的反应对官能团具有很好的容忍性和普适性,取代基可以为烷基、烷氧基、氰基、酯基、硝基、卤原子(F、Cl、Br)等;
6、本发明方法可以大量(克级)制备1,3-二取代平面手性金属茂化合物,为工业化生产奠定了良好的基础。
具体实施方式
下面通过具体实施例对本发明给予进一步说明,值得注意的是,本发明不仅限于下述的实施例。
实施例1:化合物I-1的制备
在氩气保护下,向干燥并装有磁力搅拌子的反应管中加入醋酸钯(2.2mg,0.01mmol)、(S)-2-((叔丁氧羰基)氨基)-3-甲基丁酸(6.5mg,0.03mmol),碳酸钾(27.6mg,0.2mmol)、干燥的二甲基亚砜(0.1mL)和干燥的N,N-二甲基乙酰胺(0.4mL),然后加入1-正庚基-2-降冰片烯(8.3mg,0.05mmol)、N,N-二甲基氨甲基二茂铁(24.3mg,0.1mmol)、4-碘-苯甲酸甲酯(31.4mg,0.12mmol)。所得混合物于80℃在氩气保护氛围下反应18小时。反应结束后冷却至室温,向反应液中加入10mL饱和的碳酸钠溶液淬灭反应,乙酸乙酯(10mL×3)萃取,有机相经水以及饱和食盐水洗涤,无水硫酸钠干燥后,减压蒸馏除去溶剂,柱层析分离纯化得化合物I-1(红色油状液体,82%产率,>99%ee)。1H NMR(400MHz,CDCl3):δ8.00–7.88(m,2H),7.54–7.44(m,2H),4.76(t,J=1.5Hz,1H),4.68(t,J=2.0Hz,1H),4.44–4.37(m,1H),3.98(s,5H),3.91(s,3H),3.38(d,J=12.8Hz,1H),3.27(d,J=12.8Hz,1H),2.22(s,6H);13C NMR(100MHz,CDCl3):δ167.3,145.1,129.8,127.4,125.6,85.5,83.4,71.9,70.5,69.0,66.9,59.3,52.1,45.0;HRMS(ESI-TOF):calc’d for C21H23FeNO2 +[M+]377.1073,found 377.1075;HPLC:>99%ee,Daicel Chiralpak IA column,Hexanes/IPA/Et2NH=95/5/0.1,0.7mL/min,λ=254nm,tR(major)=23.160min;109.89(c 0.44,CHCl3).
操作步骤同实施例1,区别在于所使用的亲电试剂为芳基溴化物:4-溴-苯甲酸甲酯(43.0mg),反应溶剂为N,N-二甲基乙酰胺(0.5mL),反应混合物于80℃在空气氛围下反应24小时,得化合物I-1(63%产率,>99%ee)。
实施例2:化合物I-2的制备
操作步骤同实施例1,区别在于所使用的芳基碘化物为:4-氟碘苯(26.5mg),得化合物I-2(红色油状液体,66%产率)。1H NMR(400MHz,CDCl3):δ7.46–7.34(m,2H),6.97(t,J=8.7Hz,2H),4.65(t,J=1.5Hz,1H),4.56(t,J=2.0Hz,1H),4.33(t,J=1.9Hz,1H),3.99(s,5H),3.42(d,J=12.9Hz,1H),3.32(d,J=12.8Hz,1H),2.24(s,6H);13C NMR(100MHz,CDCl3):δ161.5(d,J=243.0Hz),134.9(d,J=3.0Hz),127.5(d,J=8.0Hz),115.4(d,J=21.0Hz),85.1,83.8,71.1,70.3,68.7,66.5,59.2,44.7;19F NMR(376MHz,CDCl3):δ-116.9;HRMS(ESI+FTMS):calc’d for C19H21FFeN+[M+H+]338.1002,found 338.0997;HPLC:>99%ee,Daicel Chiralpak OD-H column,Hexanes/IPA/Et2NH=99/1/0.1,0.5mL/min,λ=254nm,tR(major)=14.397min;52.24(c 1.07,CHCl3).
实施例3:化合物I-3的制备
操作步骤同实施例1,区别在于所使用的芳基碘化物为:4-氯碘苯(28.4mg),得化合物I-3(黄色油状液体,60%产率)。1H NMR(400MHz,CDCl3):δ7.41–7.34(m,2H),7.27–7.21(m,2H),4.66(t,J=1.5Hz,1H),4.58(dd,J=2.4,1.5Hz,1H),4.34(dd,J=2.5,1.4Hz,1H),3.98(s,5H),3.37(d,J=12.8Hz,1H),3.26(d,J=12.8Hz,1H),2.22(s,6H);13C NMR(100MHz,CDCl3):δ137.9,131.5,128.6,127.2,84.8,84.3,71.3,70.4,68.6,66.5,59.3,45.0;HRMS(ESI-TOF):calc’d for C19H20ClFeN+[M+]353.0628,found 353.0632;HPLC:>99%ee,Daicel Chiralpak OD-H column,Hexanes/IPA/Et2NH=99/1/0.1,0.5mL/min,λ=254nm,tR(major)=14.506min;45.51(c 0.83CHCl3).
实施例4:化合物I-4的制备
操作步骤同实施例1,区别在于所使用的芳基碘化物为:4-溴碘苯(33.8mg),得化合物I-4(黄色油状液体,60%产率)。1H NMR(400MHz,CDCl3):δ7.41–7.34(m,2H),7.27–7.21(m,2H),4.66(t,J=1.5Hz,1H),4.58(dd,J=2.4,1.5Hz,1H),4.34(dd,J=2.5,1.4Hz,1H),3.98(s,5H),3.37(d,J=12.8Hz,1H),3.26(d,J=12.8Hz,1H),2.22(s,6H);13C NMR(100MHz,CDCl3):δ137.9,131.5,128.6,127.2,84.8,84.3,71.3,70.4,68.6,66.5,59.3,45.0;HRMS(ESI-TOF):calc’d for C19H20ClFeN+[M+]353.0628,found 353.0632;HPLC:>99%ee,Daicel Chiralpak OD-H column,Hexanes/IPA/Et2NH=99/1/0.1,0.5mL/min,λ=254nm,tR(major)=14.893min;66.88(c 0.80,CHCl3).
操作步骤同实施例1,区别在于所使用的亲电试剂为芳基溴化物:1,4-二溴苯(47.2mg),反应溶剂为N,N-二甲基乙酰胺(0.5mL),反应混合物于80℃在空气氛围下反应24小时,得化合物I-4(48%产率,>99%ee)。
实施例5:化合物I-5的制备
操作步骤同实施例1,区别在于所使用的芳基碘化物为:1,4-二碘苯(39.5mg),得化合物I-5(黄色油状液体,39%产率)。1H NMR(400MHz,CDCl3):δ7.61–7.54(m,2H),7.22–7.16(m,2H),4.67(d,J=1.5Hz,1H),4.61–4.55(m,1H),4.35(dd,J=2.5,1.4Hz,1H),3.98(s,5H),3.40(d,J=12.8Hz,1H),3.28(d,J=12.8Hz,1H),2.23(s,6H);13C NMR(100MHz,CDCl3):δ139.0,137.5,127.9,90.7,84.6,84.3,71.4,70.4,68.6,66.5,59.3,44.9;HRMS(ESI-TOF):calc’d for C19H20IFeN+[M+]444.9984,found 444.9984;HPLC:>99%ee,DaicelChiralpak OD-H column,Hexanes/IPA/Et2NH=99/1/0.1,0.5mL/min,λ=254nm,tR(major)=15.207min; 61.95(c 1.28,CHCl3).
实施例6:化合物I-6的制备
操作步骤同实施例1,区别在于所使用的芳基碘化物为:碘苯(24.5mg),得化合物I-6(红色油状液体,62%产率)。1H NMR(400MHz,CDCl3)δ7.49–7.43(m,2H),7.30–7.25(m,2H),7.20–7.14(m,1H),4.69(t,J=1.5Hz,1H),4.64–4.58(m,1H),4.32(dd,J=2.5,1.5Hz,1H),3.99(s,5H),3.37(d,J=12.8Hz,1H),3.28(d,J=12.8Hz,1H),2.22(s,6H).13C NMR(100MHz,CDCl3)δ139.1,128.4,126.1,126.0,85.6,84.6,71.0,70.3,68.7,66.5,59.4,45.0;HRMS(ESI-TOF):calc’dfor C19H21FeN+[M+]319.1018,found 319.1019;HPLC:>99%ee,Daicel Chiralpak OD-H column,Hexanes/IPA/Et2NH=99/1/0.1,0.5mL/min,λ=254nm,tR(major)=14.815min;40.13(c 1.60,CHCl3).
实施例7:化合物I-7的制备
操作步骤同实施例1,区别在于所使用的芳基碘化物为:4-甲基碘苯(26.2mg),得化合物I-7(黄色油状液体,62%产率)。1H NMR(400MHz,CDCl3):δ7.36(d,J=8.2Hz,2H),7.09(d,J=7.8Hz,2H),4.66(t,J=1.5Hz,1H),4.57(dd,J=2.5,1.5Hz,1H),4.30(dd,J=2.4,1.4Hz,1H),3.98(s,5H),3.37(d,J=12.8Hz,1H),3.27(d,J=12.8Hz,1H),2.32(s,3H).2.22(s,6H);13C NMR(100MHz,CDCl3)δ136.0,135.6,129.2,126.1,85.9,84.3,70.8,70.2,68.6,66.3,59.5,45.0,21.3;HRMS(ESI-TOF):calc’d for C20H23FeN+[M+]333.1174,found 333.1176;HPLC:>99%ee,Daicel Chiralpak OD-H column,Hexanes/IPA/Et2NH=99/1/0.1,0.5mL/min,λ=254nm,tR(major)=13.263min;6.78(c 0.52,CHCl3).
实施例8:化合物I-8的制备
操作步骤同实施例1,区别在于所使用的芳基碘化物为:4-甲氧基碘苯(28.1mg),得化合物I-8(黄色油状液体,51%产率)。1H NMR(400MHz,CDCl3)δ7.42–7.36(m,2H),6.87–6.80(m,2H),4.62(t,J=1.5Hz,1H),4.54(dd,J=2.4,1.5Hz,1H),4.28(dd,J=2.4,1.4Hz,1H),3.98(s,5H),3.82(s,3H),3.37(d,J=12.8Hz,1H),3.27(d,J=12.8Hz,1H),2.22(s,6H);13C NMR(100MHz,CDCl3)δ158.1,131.2,127.2,114.0,86.0,84.1,70.6,70.2,68.4,66.1,59.5,55.4,45.0;HRMS(ESI-TOF):calc’d for C20H23FeNO+[M+]349.1124,found349.1132;HPLC:>99%ee,Daicel Chiralpak OD-H column,Hexanes/IPA/Et2NH=99/1/0.1,0.5mL/min,λ=254nm,tR(major)=19.538min;52.20(c 0.89,CHCl3);
实施例9:化合物I-9的制备
操作步骤同实施例1,区别在于所使用的芳基碘化物为:4-三氟甲氧基碘苯(34.6mg),得化合物I-9(红色油状液体,60%产率)。1H NMR(400MHz,CDCl3)δ7.49–7.41(m,2H),7.15–7.08(m,2H),4.66(t,J=1.5Hz,1H),4.58(dd,J=2.5,1.5Hz,1H),4.35(dd,J=2.5,1.4Hz,1H),4.00(s,5H),3.38(d,J=12.8Hz,1H),3.27(d,J=12.8Hz,1H),2.22(s,6H);13C NMR(100MHz,CDCl3)δ147.4(d,J=2.0Hz),138.2,127.2,121.1,,120.6(q,J=255Hz),84.9,84.1,71.3,70.4,68.8,66.60,59.3,45.0;19F NMR(376MHz,CDCl3):δ-57.84;HRMS(ESI-TOF):calc’d for C20H21F3FeNO+[M+]403.0841,found 403.0844;HPLC:>99%ee,Daicel Chiralpak IA column,Hexanes/IPA/Et2NH=95/5/0.1,0.7mL/min,λ=254nm,tR(major)=9.744min;57.16(c 0.85,CHCl3).
操作步骤同实施例1,区别在于所使用的亲电试剂为芳基溴化物:1-溴-4-三氟甲氧基苯(48.2mg),反应溶剂为N,N-二甲基乙酰胺(0.5mL),反应混合物于80℃在空气氛围下反应24小时,得化合物I-9(42%产率,>99%ee)。
实施例10:化合物I-10的制备
操作步骤同实施例1,区别在于所使用的芳基碘化物为:4-碘苯基-4-甲基苯磺酸酯(44.9mg),得化合物I-10(红色油状液体,54%产率)。1H NMR(400MHz,CDCl3):δ7.70(d,J=8.2Hz,2H),7.37–7.27(m,4H),6.92–6.79(m,2H),4.63(s,1H),4.54(t,J=2.0Hz,1H),4.33(t,J=1.9Hz,1H),3.95(s,5H),3.36(d,J=12.8Hz,1H),3.26(d,J=12.8Hz,1H),2.43(s,3H),2.21(s,6H);13C NMR(100MHz,CDCl3):δ147.7,145.4,138.4,132.5,129.8,128.7,126.9,122.4,84.7,84.0,71.4,70.4,68.7,66.6,59.2,44.8,21.8;HRMS(ESI-TOF):calc’dfor C26H27FeNO3S+[M+]489.1056,found 489.1060;HPLC:>99%ee,Daicel Chiralpak OJcolumn,Hexanes/IPA=85/15,1.0mL/min,λ=254nm,tR(major)=30.151min;34.14(c 1.86,CHCl3).
实施例11:化合物I-11的制备
操作步骤同实施例1,区别在于所使用的芳基碘化物为:4-碘苯甲硫醚(30.0mg),得化合物I-11(红色油状液体,59%产率)。1H NMR(400MHz,CDCl3):δ7.41–7.35(m,2H),7.21–7.15(m,2H),4.66(t,J=1.5Hz,1H),4.58(dd,J=2.5,1.5Hz,1H),4.32(dd,J=2.5,1.5Hz,1H),3.98(s,5H),3.37(d,J=12.8Hz,1H),3.27(d,J=12.8Hz,1H),2.49(s,3H),2.22(s,6H);13C NMR(100MHz,CDCl3):δ136.2,135.5,127.0,126.5,85.1,84.5,71.0,70.3,68.5,66.3,59.4,44.9,16.3;HRMS(ESI-TOF):calc’d for C20H23FeNS+[M+]365.0895,found365.0896;HPLC:>99%ee,Daicel Chiralpak OD-H column,Hexanes/IPA/Et2NH=99/1/0.1,0.5mL/min,λ=254nm,tR(major)=18.968min;88.96(c 0.67,CHCl3).
实施例12:化合物I-12的制备
操作步骤同实施例1,区别在于所使用的芳基碘化物为:4-碘联苯(33.6mg),得化合物I-12(黄色油状液体,59%产率)。1H NMR(400MHz,CDCl3):δ7.66–7.60(m,2H),7.57–7.50(m,4H),7.45(t,J=7.6Hz,2H),7.38–7.32(m,1H),4.74(t,J=1.5Hz,1H),4.68–4.63(m,1H),4.40–4.33(m,1H),4.03(s,5H),3.41(d,J=12.8Hz,1H),3.31(d,J=12.8Hz,1H),2.25(s,6H);13C NMR(100MHz,CDCl3):δ141.0,138.7,138.3,128.9,127.2,127.1,126.9,126.5,85.1,84.5,71.1,70.3,68.7,66.5,59.4,44.9;HRMS(ESI-TOF):calc’d forC25H25FeN+[M+]395.1331,found395.1333;HPLC:>99%ee,Daicel Chiralpak OD-H column,Hexanes/IPA/Et2NH=99/1/0.1,0.5mL/min,λ=254nm,tR(major)=18.392min;71.12(c 0.89,CHCl3).
实施例13:化合物I-13的制备
操作步骤同实施例1,区别在于所使用的芳基碘化物为:4-碘苯甲醛(27.8mg),得化合物I-13(红色油状液体,73%产率)。1H NMR(400MHz,CDCl3):δ9.96(s,1H),7.78(d,J=8.0Hz,2H),7.57(d,J=8.0Hz,2H),4.79(d,J=1.4Hz,1H),4.71(dd,J=2.6,1.4Hz,1H),4.49–4.40(m,1H),4.00(s,5H),3.39(d,J=12.8Hz,1H),3.28(d,J=12.8Hz,1H),2.23(s,6H);13C NMR(100MHz,CDCl3):δ191.9,147.3,134.1,130.1,126.1,85.9,82.9,72.3,70.6,69.2,67.1,59.3,45.0;HRMS(ESI-TOF):calc’d for C20H21FeNO+[M+]347.0967,found347.0971;HPLC:>99%ee,Daicel Chiralpak OD-H column,Hexanes/IPA=90/10,1.0mL/min,λ=254nm,tR(major)=9.425min;84.86(c 0.89,CHCl3).
操作步骤同实施例1,区别在于所使用的亲电试剂为芳基溴化物:4-溴苯甲醛(37.0mg),反应溶剂为N,N-二甲基乙酰胺(0.5mL),反应混合物于80℃在空气氛围下反应24小时,得化合物I-13(80%产率,>99%ee)。
实施例14:化合物I-14的制备
操作步骤同实施例1,区别在于所使用的芳基碘化物为:4-碘苯乙酮(29.5mg),得化合物I-14(红色油状液体,62%产率)。1H NMR(400MHz,CDCl3):δ7.87(d,J=8.5Hz,2H),7.51(d,J=8.5Hz,2H),4.77(t,J=1.4Hz,1H),4.69(dd,J=2.5,1.5Hz,1H),4.42(dd,J=2.5,1.4Hz,1H),3.99(s,5H),3.39(d,J=12.8Hz,1H),3.27(d,J=12.8Hz,1H),2.59(s,3H),2.23(s,6H);13C NMR(100MHz,CDCl3):δ197.8,145.5,134.7,128.7,125.8,86.0,83.3,72.0,70.6,69.1,67.0,59.3,45.0,26.7;HRMS(ESI-TOF):calc’d for C21H23FeNO+[M+]361.1124,found361.1126;HPLC:>99%ee,Daicel Chiralpak IA column,Hexanes/IPA/Et2NH=95/5/0.1,1.0mL/min,λ=254nm,tR(major)=30.554min;63.62(c 0.58,CHCl3).
操作步骤同实施例1,区别在于所使用的亲电试剂为芳基溴化物:4-溴苯乙酮(39.8mg),反应溶剂为N,N-二甲基乙酰胺(0.5mL),反应混合物于80℃在空气氛围下反应24小时,得化合物I-14(68%产率,>99%ee)。
实施例15:化合物I-15的制备
操作步骤同实施例1,区别在于所使用的芳基碘化物为:4-碘苯甲腈(27.5mg),得化合物I-15(红色油状液体,47%产率)。1H NMR(400MHz,CDCl3):δ7.54(d,J=8.6Hz,2H),7.50(d,J=8.7Hz,2H),4.75(t,J=1.5Hz,1H),4.66(dd,J=2.5,1.5Hz,1H),4.44(dd,J=2.6,1.4Hz,1H),4.00(s,5H),3.39(d,J=12.8Hz,1H),3.26(d,J=12.8Hz,1H),2.23(s,6H);13C NMR(100MHz,CDCl3):δ145.5,132.3,126.2,119.5,108.9,86.0,82.5,72.3,70.6,69.0,67.0,59.2,45.0;HRMS(ESI-TOF):calc’d for C20H20FeN2 +[M+]344.0970,found344.0975;HPLC:98%ee,Daicel Chiralpak IA column,Hexanes/IPA/Et2NH=95/5/0.1,0.7mL/min,λ=254nm,tR(major)=27.223min,tR(minor)=31.369min;100.64(c0.47,CHCl3).
操作步骤同实施例1,区别在于所使用的亲电试剂为芳基溴化物:4-溴苯甲腈(36.4mg),反应溶剂为N,N-二甲基乙酰胺(0.5mL),反应混合物于80℃在空气氛围下反应24小时,得化合物I-15(67%产率,>99%ee)。
实施例16:化合物I-16的制备
操作步骤同实施例1,区别在于所使用的芳基碘化物为:4-碘硝基苯(29.9mg),得化合物I-16(红色油状液体,77%产率)。1H NMR(400MHz,CDCl3):δ8.19–8.07(m,2H),7.61–7.45(m,2H),4.80(d,J=1.5Hz,1H),4.73–4.68(m,1H),4.49(dd,J=2.5,1.4Hz,1H),4.01(s,5H),3.39(d,J=12.8Hz,1H),3.27(d,J=12.9Hz,1H),2.24(s,6H);13C NMR(100MHz,CDCl3):δ148.1,145.7,126.0,124.0,86.5,81.9,72.6,70.7,69.3,67.3,59.2,45.0;HRMS(ESI+FTMS):calc’d for C19H21FeN2O2 +[M+H+]365.0947,found 365.0937;HPLC:97%ee,Daicel Chiralpak OD-H column,Hexanes/IPA=7/3,1.0mL/min,λ=220nm,tR(major)=6.238min,tR(minor)=9.794min;252.63(c 0.02,CHCl3).
操作步骤同实施例1,区别在于所使用的亲电试剂为芳基溴化物:1-溴-4-硝基苯(40.2mg),反应溶剂为N,N-二甲基乙酰胺(0.5mL),反应混合物于80℃在空气氛围下反应24小时,得化合物I-16(78%产率,>99%ee)。
实施例17:化合物I-17的制备
操作步骤同实施例1,区别在于所使用的芳基碘化物为:4-三氟甲基碘苯(32.6mg),得化合物I-17(红色油状液体,68%产率)。1H NMR(400MHz,CDCl3):δ7.58–7.46(m,4H),4.75(d,J=1.5Hz,1H),4.66(dd,J=2.5,1.5Hz,1H),4.41(dd,J=2.5,1.4Hz,1H),4.00(s,5H),3.42(d,J=12.9Hz,1H),3.30(d,J=12.8Hz,1H),2.25(s,6H);13C NMR(100MHz,CDCl3):δ143.6,127.8(q,J=32.0Hz),126.0,125.4(q,J=4.0Hz),124.6(q,J=262.6Hz),85.0,83.5,71.8,70.5,69.0,66.9,59.2,44.9;19F NMR(376MHz,CDCl3):δ-62.36;HRMS(ESI-TOF):calc’d for C20H20F3FeN+[M+]387.0892,found 387.0895;HPLC:99%ee,Daicel Chiralpak IA column,Hexanes/IPA/Et2NH=95/5/0.1,0.7mL/min,λ=254nm,tR(major)=10.953min,tR(minor)=13.750min;73.28(c 0.66,CHCl3).
操作步骤同实施例1,区别在于所使用的亲电试剂为芳基溴化物:1-溴-4-三氟甲苯(45.0mg),反应溶剂为N,N-二甲基乙酰胺(0.5mL),反应混合物于80℃在空气氛围下反应24小时,得化合物I-17(80%产率,>99%ee)
实施例18:化合物I-18的制备
操作步骤同实施例1,区别在于所使用的芳基碘化物为:N-甲氧基-N-甲基-4-碘苯甲酰(34.9mg),得化合物I-18(红色油状液体,68%产率)。1H NMR(400MHz,CDCl3):δ7.62(d,J=8.2Hz,2H),7.46(d,J=8.2Hz,2H),4.73(d,J=1.5Hz,1H),4.68–4.61(m,1H),4.37(dd,J=2.5,1.4Hz,1H),3.98(s,5H),3.58(s,3H),3.38(d,J=12.8Hz,1H),3.37(s,3H),3.28(d,J=12.8Hz,1H),2.22(s,6H);13CNMR(100MHz,CDCl3):δ169.9,142.4,131.2,128.7,125.4,85.1,84.0,71.6,70.4,68.9,66.7,61.1,59.3,45.0,34.1;HRMS(ESI-TOF):calc’dfor C22H26FeN2O2 +[M+]406.1338,found 406.1337;HPLC:99%ee,Daicel Chiralpak IAcolumn,Hexanes/IPA/Et2NH=95/5/0.1,0.7mL/min,λ=254nm,tR(major)=10.953min,tR(minor)=13.750min;68.14(c 0.89,CHCl3).
实施例19:化合物I-19的制备
操作步骤同实施例1,区别在于所使用的芳基碘化物为:2-氟碘苯(26.6mg),得化合物I-19(黄色油状液体,41%产率)。1H NMR(400MHz,CDCl3):δ7.48(td,J=7.7,1.7Hz,1H),7.21–7.12(m,1H),7.10–6.98(m,2H),4.79(q,J=1.6Hz,1H),4.72(q,J=1.9Hz,1H),4.36(dd,J=2.6,1.5Hz,1H),4.03(s,5H),3.42(d,J=12.9Hz,1H),3.36(d,J=12.9Hz,1H),2.25(s,6H);13C NMR(100MHz,CDCl3):δ160.1(d,J=249.5Hz),128.9(d,J=5.0Hz),127.4(d,J=249.5Hz),126.7(d,J=13.0Hz),124.2(d,J=3.0Hz),116.1(d,J=23.2Hz),84.0,80.1,71.3,70.5(d,J=5.0Hz),70.4,68.4(d,J=5.0Hz),59.3,44.8;19F NMR(376MHz,CDCl3):δ-113.71;HRMS(ESI+FTMS):calc’d for C19H21FFeN+[M+H+]338.1002,found338.0992;HPLC:>99%ee,Daicel Chiralpak IG column,Hexanes/IPA/Et2NH=99/1/0.1,1.0mL/min,λ=254nm,tR(major)=20.905min;75.61(c 0.29,CHCl3).
实施例20:化合物I-20的制备
操作步骤同实施例1,区别在于所使用的芳基碘化物为:2-氟-4-碘-苯腈(29.6mg),得化合物I-20(红色固体,95%产率)。Melting point:164-165℃;1H NMR(400MHz,CDCl3):δ7.48(dd,J=8.1,6.7Hz,1H),7.29–7.26(m,1H),7.21(dd,J=10.5,1.6Hz,1H),4.73(t,J=1.5Hz,1H),4.65(dd,J=2.6,1.5Hz,1H),4.47(dd,J=2.6,1.4Hz,1H),4.01(s,5H),3.37(d,J=12.8Hz,1H),3.25(d,J=12.8Hz,1H),2.22(s,6H);13C NMR(100MHz,CDCl3):δ163.5(d,J=257.4Hz),149.1(d,J=8.6Hz),133.3,121.9(d,J=2.9Hz),114.7,112.9(d,J=20.3Hz),97.7(d,J=15.7Hz),86.4,81.2(d,J=2.3Hz),72.7,70.8,69.2,67.2,59.1,45.0;19F NMR(376MHz,CDCl3):δ-107.39;HRMS(ESI+FTMS):calc’dfor C20H20FFeN2 +[M+H+]363.0954,found 363.0946;HPLC:>99%ee,Daicel Chiralpak IAcolumn,Hexanes/IPA/Et2NH=95/5/0.1,0.7mL/min,λ=254nm,tR(major)=26.951min;138.35(c 0.28,CHCl3).
实施例21:化合物I-21的制备
操作步骤同实施例1,区别在于所使用的金属茂化合物为:1-N,N-二甲基氨甲基-1'-甲基二茂钌(30.2mg),得化合物I-21(无色油状物,80%产率)。1H NMR(400MHz,CDCl3):δ7.88(d,J=8.1Hz,2H),7.37(d,J=8.1Hz,2H),5.12(s,1H),5.05–4.99(m,1H),4.72(t,J=1.6Hz,1H),4.42–4.34(m,2H),4.29(d,J=1.8Hz,2H),3.89(s,3H),3.18(d,J=12.9Hz,1H),3.07(d,J=12.9Hz,1H),2.28(s,6H),1.53(s,3H);13C NMR(100MHz,CDCl3):δ167.2,143.6,129.8,127.3,125.4,87.82,87.76,87.7,74.2,73.73,73.67,71.9,69.8,58.9,52.1,44.8,13.3;19F NMR(376MHz,CDCl3):δ-107.39;HRMS(ESI+FTMS):calc’d forC22H26NO2Ru+[M+H+]438.1002,found 438.1000.,found 363.0946;HPLC:>99%ee,DaicelChiralpak IA column,Hexanes/IPA/Et2NH=97/3/0.1,0.7mL/min,λ=254nm,tR(major)=21.752min;8.89(c 0.72,CHCl3).
实施例22:化合物I-22的制备
操作步骤同实施例1,区别在于所使用的金属茂化合物为:1-N,N-二甲基氨甲基-1'-(4,4,5,5-四甲基-1,3-1,3-二氧戊环-2-基)二茂钌(41.6mg),得化合物I-22(黄色固体,45%产率)。Melting point:95-96℃;1H NMR(400MHz,CDCl3):δ7.87(d,J=8.1Hz,2H),7.44(d,J=8.1Hz,2H),5.31(s,1H),5.18(s,1H),5.06(d,J=2.4Hz,1H),4.78(d,J=2.4Hz,1H),4.60–4.50(m,2H),4.47–4.40(m,1H),4.39–4.32(m,1H),3.89(s,3H),3.25(d,J=13.1Hz,1H),3.14(d,J=13.1Hz,1H),2.29(s,6H),1.17(s,6H),1.15(s,6H);13C NMR(100MHz,CDCl3):δ167.2,143.7,129.6,127.6,126.0,98.0,90.6,88.8,88.1,82.4,74.6,73.0,72.7,72.7,71.5,71.3,70.5,58.8,52.1,44.7,24.3,22.1;HRMS(ESI+FTMS):calc’dfor C28H36NO4Ru+[M+H+]552.1682,found 552.1673;HPLC:99%ee,Daicel ChiralpakAD-Hcolumn,Hexanes/IPA/Et2NH=95/5/0.1,1.0mL/min,λ=280nm,tR(major)=24.339min,tR(minor)=19.486min;35.89(c 1.07,CHCl3).
实施例23:化合物I-20的克级制备
在氩气保护下,向干燥并装有磁力搅拌子的反应管中加入醋酸钯(78.4mg,0.35mmol)、(S)-2-((叔丁氧羰基)氨基)-3-甲基丁酸(227.9mg,1.05mmol)碳酸钾(970mg,7.0mmol)、干燥的二甲基亚砜(3.5mL)和干燥的N,N-二甲基乙酰胺(14mL),然后加入1-正庚基-2-降冰片烯(339.5mg,1.75mmol)、N,N-二甲基氨甲基二茂铁(850.5mg,3.5mmol)、2-氟-4-碘-苯腈(1.04g,4.2mmol)。所得混合物于80℃在氩气保护氛围下反应36小时。反应结束后冷却至室温,相反应液中加入50mL饱和的碳酸钠溶液淬灭反应,乙酸乙酯(50mL×3)萃取,有机相经水以及饱和食盐水洗涤,无水硫酸钠干燥后,减压蒸馏除去溶剂,柱层析分离纯化得化合物I-20(1.12g,红色油状液体,89%产率,98%ee)。
以上所述,仅为本发明较佳的具体实施方式,但本发明保护的范围并不局限于此,任何熟悉本技术领域的技术人员在本发明揭露的技术范围内所做的任何修改,等同替换和改进等,均应包含在发明的保护范围之内。
Claims (4)
1.一种合成1,3-二取代平面手性金属茂化合物的方法,其特征在于,包括以下步骤:
以N,N-烷基氨基甲基二茂铁/钌A和芳基卤化物B为起始原料,在钯催化剂C、手性氨基酸D、降冰片烯衍生物E和碱F的作用下,于有机溶剂G中搅拌反应直至反应结束,将反应混合物后处理,即得到如式I的1,3-二取代平面手性金属茂化合物,
所述反应式如下:
其中:
R1,R2为烷基,两个基团相同或不同,或者相互连接;
R3选自氢、烷基、缩醛基;
X为溴或者碘;
M为铁或者钌;
R4选自芳基、杂环芳基、烷基、酯基、醛基、羟基、硅基、氨基、氰基、硝基、酰胺基、磺酰基、烷氧基、烯基、炔基、卤素中的一种或几种;
m表示R4的个数,0≤m≤2;当m=2时,两个基团相同或不同;
Ar1为芳烃;
所述钯催化剂C为Pd(OAc)2;
所述手性氨基酸D为(S)-2-((叔丁氧羰基)氨基)-3-甲基丁酸;
所述降冰片烯衍生物E为1-正庚基-2-降冰片烯;
所述碱F为碳酸钾;
所述溶剂G选自二甲基亚砜或N,N-二甲基乙酰胺。
2.根据权利要求1所述的一种合成1,3-二取代平面手性金属茂化合物的方法,其特征在于,反应在空气、氧气或惰性气体保护下进行。
3.根据权利要求2所述的一种合成1,3-二取代平面手性金属茂化合物的方法,其特征在于,反应在惰性气体保护下进行。
4.根据权利要求1所述的一种合成1,3-二取代平面手性金属茂化合物的方法,其特征在于,所述后处理方法为:将反应混合物过滤、浓缩、柱层析纯化即得到如式I的1,3-二取代平面手性金属茂化合物。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202210052476.4A CN114409714B (zh) | 2022-01-18 | 2022-01-18 | 一种合成1,3-二取代平面手性金属茂化合物的方法 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202210052476.4A CN114409714B (zh) | 2022-01-18 | 2022-01-18 | 一种合成1,3-二取代平面手性金属茂化合物的方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN114409714A CN114409714A (zh) | 2022-04-29 |
CN114409714B true CN114409714B (zh) | 2024-02-06 |
Family
ID=81272491
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202210052476.4A Active CN114409714B (zh) | 2022-01-18 | 2022-01-18 | 一种合成1,3-二取代平面手性金属茂化合物的方法 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN114409714B (zh) |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB9216514D0 (en) * | 1992-08-04 | 1992-09-16 | Secr Defence | Ferrocene compounds,materials and devices containing such compounds and materials |
JPH10237083A (ja) * | 1996-12-25 | 1998-09-08 | Nichia Chem Ind Ltd | メタロセン化合物の合成方法 |
WO2007033937A1 (en) * | 2005-09-19 | 2007-03-29 | Basell Polyolefine Gmbh | Synthesis of cyclopentadienedithiophene derivatives |
CN102964390A (zh) * | 2012-11-27 | 2013-03-13 | 中国科学院上海有机化学研究所 | 一种平面手性二茂铁化合物、合成方法及用途 |
CN105254682A (zh) * | 2015-11-10 | 2016-01-20 | 中国科学院上海有机化学研究所 | 一种平面手性二茂铁化合物、合成方法及用途 |
-
2022
- 2022-01-18 CN CN202210052476.4A patent/CN114409714B/zh active Active
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB9216514D0 (en) * | 1992-08-04 | 1992-09-16 | Secr Defence | Ferrocene compounds,materials and devices containing such compounds and materials |
JPH10237083A (ja) * | 1996-12-25 | 1998-09-08 | Nichia Chem Ind Ltd | メタロセン化合物の合成方法 |
WO2007033937A1 (en) * | 2005-09-19 | 2007-03-29 | Basell Polyolefine Gmbh | Synthesis of cyclopentadienedithiophene derivatives |
CN102964390A (zh) * | 2012-11-27 | 2013-03-13 | 中国科学院上海有机化学研究所 | 一种平面手性二茂铁化合物、合成方法及用途 |
CN105254682A (zh) * | 2015-11-10 | 2016-01-20 | 中国科学院上海有机化学研究所 | 一种平面手性二茂铁化合物、合成方法及用途 |
Non-Patent Citations (5)
Title |
---|
"Bromide-Mediated ortho-Deprotonation in the Synthesis of Chiral, Nonracemic Ferrocene Derivatives";Steurer, Marianne等;《Organometallics》;第26卷(第15期);第3850–3859页 * |
"Catalytic Asymmetric Synthesis of Ferrocenes and P-Stereogenic Bisphosphines";Genet, Cédric等;《Journal of the American Chemical Society》;第128卷(第29期);第9336–9337页 * |
"From 2- to 3-substituted ferrocene carboxamides or how to apply halogen "dance" to the ferrocene series";Tazi, Mehdi 等;《Organometallics》;第36卷(第24期);第4770-4778页 * |
"基于钯/降冰片烯共催化的串联反应构建轴手性化合物";丁琳琳;《中国优秀硕士论文全文数据库(电子期刊)工程科技Ⅰ辑》(第12期);第B014-58页 * |
"过渡金属催化法合成平面手性二茂铁衍生物的新进展";王艳芳 等;《有机化学》;第35卷(第07期);第1399-1406页 * |
Also Published As
Publication number | Publication date |
---|---|
CN114409714A (zh) | 2022-04-29 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN108299423B (zh) | 一种二氢吡咯并2-氨基喹啉类化合物的合成方法 | |
CN113563370B (zh) | 一种壳聚糖负载铜材料催化制备α位有取代基的β-硼基酮的制备方法 | |
CN111423381B (zh) | 一种2-三氟甲基取代的咪唑化合物的制备方法 | |
CN111718372B (zh) | 一种轴手性膦-烯配体及其制备方法与应用 | |
JP7464234B2 (ja) | 軸不斉を有する高光学活性アレンカルボン酸系化合物を製造する方法 | |
CN111592507A (zh) | 一种绿色简单制备多取代呋喃的新方法 | |
CN113880822B (zh) | 一种手性含亚胺喹啉噁唑啉类化合物及其金属络合物以及制备方法和应用 | |
CN114409714B (zh) | 一种合成1,3-二取代平面手性金属茂化合物的方法 | |
CN116253721B (zh) | 一类n-(4-吲哚基)-n’-烷基咪唑盐及其应用 | |
CN112898259B (zh) | 一种非金属催化氢化制备3位取代色满酮的方法 | |
CN113735778A (zh) | 一种5-三氟甲基取代的咪唑化合物的制备方法 | |
CN116947695A (zh) | 一种1,3,6-己烷三腈的制备方法和应用 | |
CN114989063B (zh) | 一种β-卤代吡咯类化合物的合成方法 | |
CN113511986B (zh) | 一种芳基乙腈类衍生物的制备方法 | |
CN113416162B (zh) | 一种双手性联萘o-n-n三齿配体及其制备方法 | |
CN115108937A (zh) | 含三级立体中心的α-叠氮酮的合成方法 | |
CN111116450B (zh) | 一种轴手性萘胺方酰胺类有机催化剂及其制备方法和应用 | |
CN108250206B (zh) | 一种联芳木脂素类化合物及其中间体的合成方法 | |
CN112694430A (zh) | 一种1,5-二氢-2h-吡咯-2-酮化合物的制备方法 | |
Ashokkumar et al. | A new series of bipyridine based chiral organocatalysts for enantioselective Henry reaction | |
CN117362358A (zh) | 一种平面手性碘代茂金属及其制备方法和制备多取代平面手性茂金属化合物的方法 | |
CN111732541B (zh) | 一种钌催化的c-h活化/环合反应高效合成6-烯基菲啶衍生物的方法 | |
CN112679431B (zh) | 一种制备异喹啉酮类化合物的方法 | |
US9340519B2 (en) | Paracyclophane-based ligands, their preparation and use in catalysis | |
CN114989137B (zh) | 一种手性含亚胺喹啉咪唑啉类化合物及其金属络合物以及制备方法和应用 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |