CN118026834A - Preparation method of planar chiral indene metal complex with phenylindene skeleton, synthesis intermediate and catalytic application - Google Patents
Preparation method of planar chiral indene metal complex with phenylindene skeleton, synthesis intermediate and catalytic application Download PDFInfo
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- CN118026834A CN118026834A CN202410177087.3A CN202410177087A CN118026834A CN 118026834 A CN118026834 A CN 118026834A CN 202410177087 A CN202410177087 A CN 202410177087A CN 118026834 A CN118026834 A CN 118026834A
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- Prior art keywords
- chiral
- indene
- configuration
- formula
- metal complex
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- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 title claims abstract description 233
- -1 indene metal complex Chemical class 0.000 title claims abstract description 81
- 230000015572 biosynthetic process Effects 0.000 title abstract description 32
- 238000003786 synthesis reaction Methods 0.000 title abstract description 32
- 230000003197 catalytic effect Effects 0.000 title abstract description 10
- 238000002360 preparation method Methods 0.000 title abstract description 6
- PXORBAGTGTXORO-UHFFFAOYSA-N 1-phenyl-1h-indene Chemical group C1=CC2=CC=CC=C2C1C1=CC=CC=C1 PXORBAGTGTXORO-UHFFFAOYSA-N 0.000 title description 5
- 239000003446 ligand Substances 0.000 claims abstract description 64
- 238000006243 chemical reaction Methods 0.000 claims abstract description 51
- 238000000034 method Methods 0.000 claims abstract description 51
- 239000003054 catalyst Substances 0.000 claims abstract description 29
- SNWQUNCRDLUDEX-UHFFFAOYSA-N inden-1-one Chemical compound C1=CC=C2C(=O)C=CC2=C1 SNWQUNCRDLUDEX-UHFFFAOYSA-N 0.000 claims abstract description 29
- 150000003623 transition metal compounds Chemical class 0.000 claims abstract description 16
- 239000004215 Carbon black (E152) Substances 0.000 claims abstract description 12
- 230000004913 activation Effects 0.000 claims abstract description 12
- 229930195733 hydrocarbon Natural products 0.000 claims abstract description 12
- 150000002430 hydrocarbons Chemical class 0.000 claims abstract description 12
- KXYGKDBONOVZOM-UHFFFAOYSA-N 1h-cyclopenta[a]naphthalene Chemical group C1=CC=CC2=C3CC=CC3=CC=C21 KXYGKDBONOVZOM-UHFFFAOYSA-N 0.000 claims abstract description 5
- 239000010948 rhodium Substances 0.000 claims description 57
- 239000000126 substance Substances 0.000 claims description 50
- 229910052751 metal Inorganic materials 0.000 claims description 47
- 239000002184 metal Substances 0.000 claims description 47
- 229910052703 rhodium Inorganic materials 0.000 claims description 33
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical group [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 claims description 33
- 239000012038 nucleophile Substances 0.000 claims description 13
- 230000002194 synthesizing effect Effects 0.000 claims description 13
- QNXSIUBBGPHDDE-UHFFFAOYSA-N indan-1-one Chemical compound C1=CC=C2C(=O)CCC2=C1 QNXSIUBBGPHDDE-UHFFFAOYSA-N 0.000 claims description 12
- 239000002253 acid Substances 0.000 claims description 11
- 125000000217 alkyl group Chemical group 0.000 claims description 11
- HSJKGGMUJITCBW-UHFFFAOYSA-N 3-hydroxybutanal Chemical compound CC(O)CC=O HSJKGGMUJITCBW-UHFFFAOYSA-N 0.000 claims description 10
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 10
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims description 8
- 125000003118 aryl group Chemical group 0.000 claims description 8
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 125000004404 heteroalkyl group Chemical group 0.000 claims description 8
- 125000001072 heteroaryl group Chemical group 0.000 claims description 8
- JJKMIZGENPMJRC-UHFFFAOYSA-N 3-oxo-3-propan-2-yloxypropanoic acid Chemical compound CC(C)OC(=O)CC(O)=O JJKMIZGENPMJRC-UHFFFAOYSA-N 0.000 claims description 6
- 125000004122 cyclic group Chemical group 0.000 claims description 6
- 239000007800 oxidant agent Substances 0.000 claims description 6
- 150000005838 radical anions Chemical class 0.000 claims description 6
- YMGUBTXCNDTFJI-UHFFFAOYSA-N cyclopropanecarboxylic acid Chemical compound OC(=O)C1CC1 YMGUBTXCNDTFJI-UHFFFAOYSA-N 0.000 claims description 5
- 150000005673 monoalkenes Chemical class 0.000 claims description 5
- NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 claims description 4
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 claims description 4
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical group [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 4
- 150000004945 aromatic hydrocarbons Chemical class 0.000 claims description 4
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 4
- ZSWFCLXCOIISFI-UHFFFAOYSA-N endo-cyclopentadiene Natural products C1C=CC=C1 ZSWFCLXCOIISFI-UHFFFAOYSA-N 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- 230000001590 oxidative effect Effects 0.000 claims description 4
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims description 4
- 235000019260 propionic acid Nutrition 0.000 claims description 4
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 4
- 150000003464 sulfur compounds Chemical class 0.000 claims description 4
- 229910017052 cobalt Inorganic materials 0.000 claims description 3
- 239000010941 cobalt Chemical group 0.000 claims description 3
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical group [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 claims description 3
- 150000001993 dienes Chemical class 0.000 claims description 3
- 239000012433 hydrogen halide Substances 0.000 claims description 3
- 229910000039 hydrogen halide Inorganic materials 0.000 claims description 3
- 150000002504 iridium compounds Chemical class 0.000 claims description 3
- 125000001979 organolithium group Chemical group 0.000 claims description 3
- 150000002978 peroxides Chemical class 0.000 claims description 3
- 150000003284 rhodium compounds Chemical class 0.000 claims description 3
- 229910052727 yttrium Inorganic materials 0.000 claims description 3
- VWQVUPCCIRVNHF-UHFFFAOYSA-N yttrium atom Chemical group [Y] VWQVUPCCIRVNHF-UHFFFAOYSA-N 0.000 claims description 3
- 239000007818 Grignard reagent Substances 0.000 claims description 2
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical group [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 claims description 2
- 150000008305 azaarenes Chemical class 0.000 claims description 2
- 150000001869 cobalt compounds Chemical class 0.000 claims description 2
- 230000018044 dehydration Effects 0.000 claims description 2
- 238000006297 dehydration reaction Methods 0.000 claims description 2
- 150000004795 grignard reagents Chemical class 0.000 claims description 2
- 229910052741 iridium Inorganic materials 0.000 claims description 2
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical group [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052742 iron Inorganic materials 0.000 claims description 2
- 229910052746 lanthanum Chemical group 0.000 claims description 2
- FZLIPJUXYLNCLC-UHFFFAOYSA-N lanthanum atom Chemical group [La] FZLIPJUXYLNCLC-UHFFFAOYSA-N 0.000 claims description 2
- 150000002604 lanthanum compounds Chemical class 0.000 claims description 2
- 238000006722 reduction reaction Methods 0.000 claims description 2
- 229910052707 ruthenium Inorganic materials 0.000 claims description 2
- 150000003304 ruthenium compounds Chemical class 0.000 claims description 2
- 229910052706 scandium Inorganic materials 0.000 claims description 2
- SIXSYDAISGFNSX-UHFFFAOYSA-N scandium atom Chemical group [Sc] SIXSYDAISGFNSX-UHFFFAOYSA-N 0.000 claims description 2
- 150000003326 scandium compounds Chemical class 0.000 claims description 2
- 150000003748 yttrium compounds Chemical class 0.000 claims description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N hydrogen peroxide Substances OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims 1
- 150000002506 iron compounds Chemical class 0.000 claims 1
- 238000007036 catalytic synthesis reaction Methods 0.000 abstract description 3
- 230000008569 process Effects 0.000 abstract description 2
- 150000001875 compounds Chemical class 0.000 description 116
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 45
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 34
- 239000007787 solid Substances 0.000 description 25
- 239000000047 product Substances 0.000 description 22
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 21
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- 239000000243 solution Substances 0.000 description 16
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 13
- 239000012043 crude product Substances 0.000 description 13
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- 239000002904 solvent Substances 0.000 description 12
- 239000007858 starting material Substances 0.000 description 12
- 239000003153 chemical reaction reagent Substances 0.000 description 10
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 239000000460 chlorine Substances 0.000 description 9
- 238000001914 filtration Methods 0.000 description 9
- 239000011630 iodine Substances 0.000 description 9
- 229910052740 iodine Inorganic materials 0.000 description 9
- 239000003208 petroleum Substances 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- 238000010586 diagram Methods 0.000 description 8
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical group [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 8
- 150000003283 rhodium Chemical class 0.000 description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 7
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- 238000004128 high performance liquid chromatography Methods 0.000 description 7
- 239000000741 silica gel Substances 0.000 description 7
- 229910002027 silica gel Inorganic materials 0.000 description 7
- QSSXJPIWXQTSIX-UHFFFAOYSA-N 1-bromo-2-methylbenzene Chemical compound CC1=CC=CC=C1Br QSSXJPIWXQTSIX-UHFFFAOYSA-N 0.000 description 6
- GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- 238000006555 catalytic reaction Methods 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- 238000010898 silica gel chromatography Methods 0.000 description 6
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
- 238000001308 synthesis method Methods 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
- 238000005160 1H NMR spectroscopy Methods 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 238000010828 elution Methods 0.000 description 5
- 229910052739 hydrogen Chemical group 0.000 description 5
- 239000001257 hydrogen Chemical group 0.000 description 5
- FRIJBUGBVQZNTB-UHFFFAOYSA-M magnesium;ethane;bromide Chemical compound [Mg+2].[Br-].[CH2-]C FRIJBUGBVQZNTB-UHFFFAOYSA-M 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical group [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- 239000000654 additive Substances 0.000 description 4
- 230000000996 additive effect Effects 0.000 description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
- 238000004440 column chromatography Methods 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 238000000605 extraction Methods 0.000 description 4
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 4
- 229940098779 methanesulfonic acid Drugs 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 239000012299 nitrogen atmosphere Substances 0.000 description 4
- 239000012434 nucleophilic reagent Substances 0.000 description 4
- 238000010189 synthetic method Methods 0.000 description 4
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 241000147041 Guaiacum officinale Species 0.000 description 3
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 150000002170 ethers Chemical class 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 235000019253 formic acid Nutrition 0.000 description 3
- 229940091561 guaiac Drugs 0.000 description 3
- 230000014759 maintenance of location Effects 0.000 description 3
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- 239000005711 Benzoic acid Substances 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 150000001336 alkenes Chemical class 0.000 description 2
- 150000001345 alkine derivatives Chemical class 0.000 description 2
- 235000010233 benzoic acid Nutrition 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 150000004696 coordination complex Chemical class 0.000 description 2
- MGNZXYYWBUKAII-UHFFFAOYSA-N cyclohexa-1,3-diene Chemical compound C1CC=CC=C1 MGNZXYYWBUKAII-UHFFFAOYSA-N 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000003810 ethyl acetate extraction Methods 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 2
- IQZZFVDIZRWADY-UHFFFAOYSA-N isocoumarin Chemical compound C1=CC=C2C(=O)OC=CC2=C1 IQZZFVDIZRWADY-UHFFFAOYSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- NIXOIRLDFIPNLJ-UHFFFAOYSA-M magnesium;benzene;bromide Chemical compound [Mg+2].[Br-].C1=CC=[C-]C=C1 NIXOIRLDFIPNLJ-UHFFFAOYSA-M 0.000 description 2
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 238000001291 vacuum drying Methods 0.000 description 2
- GRWFGVWFFZKLTI-UHFFFAOYSA-N α-pinene Chemical compound CC1=CCC2C(C)(C)C1C2 GRWFGVWFFZKLTI-UHFFFAOYSA-N 0.000 description 2
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical group CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- JVEQWIQHHWNMQX-UHFFFAOYSA-N 1-bromo-2-ethoxybenzene Chemical group CCOC1=CC=CC=C1Br JVEQWIQHHWNMQX-UHFFFAOYSA-N 0.000 description 1
- HTDQSWDEWGSAMN-UHFFFAOYSA-N 1-bromo-2-methoxybenzene Chemical group COC1=CC=CC=C1Br HTDQSWDEWGSAMN-UHFFFAOYSA-N 0.000 description 1
- MMORVPBHAHXAHH-UHFFFAOYSA-N 1-bromo-2-propan-2-yloxybenzene Chemical group CC(C)OC1=CC=CC=C1Br MMORVPBHAHXAHH-UHFFFAOYSA-N 0.000 description 1
- BUOWTUULDKULFI-UHFFFAOYSA-N 1-bromo-3,5-ditert-butylbenzene Chemical group CC(C)(C)C1=CC(Br)=CC(C(C)(C)C)=C1 BUOWTUULDKULFI-UHFFFAOYSA-N 0.000 description 1
- GRWFGVWFFZKLTI-IUCAKERBSA-N 1S,5S-(-)-alpha-Pinene Natural products CC1=CC[C@@H]2C(C)(C)[C@H]1C2 GRWFGVWFFZKLTI-IUCAKERBSA-N 0.000 description 1
- VHVYSMMZHORFKU-UHFFFAOYSA-N 2-bromo-1,3-dimethoxybenzene Chemical group COC1=CC=CC(OC)=C1Br VHVYSMMZHORFKU-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 229910002567 K2S2O8 Inorganic materials 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- AHVYPIQETPWLSZ-UHFFFAOYSA-N N-methyl-pyrrolidine Natural products CN1CC=CC1 AHVYPIQETPWLSZ-UHFFFAOYSA-N 0.000 description 1
- RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 description 1
- QCWXUUIWCKQGHC-UHFFFAOYSA-N Zirconium Chemical compound [Zr] QCWXUUIWCKQGHC-UHFFFAOYSA-N 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 238000007259 addition reaction Methods 0.000 description 1
- 229910001413 alkali metal ion Inorganic materials 0.000 description 1
- 150000004703 alkoxides Chemical group 0.000 description 1
- MVNCAPSFBDBCGF-UHFFFAOYSA-N alpha-pinene Natural products CC1=CCC23C1CC2C3(C)C MVNCAPSFBDBCGF-UHFFFAOYSA-N 0.000 description 1
- 238000005269 aluminizing Methods 0.000 description 1
- 238000007112 amidation reaction Methods 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 238000009876 asymmetric hydrogenation reaction Methods 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- OPHUWKNKFYBPDR-UHFFFAOYSA-N copper lithium Chemical compound [Li].[Cu] OPHUWKNKFYBPDR-UHFFFAOYSA-N 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 238000005913 hydroamination reaction Methods 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- VDBNYAPERZTOOF-UHFFFAOYSA-N isoquinolin-1(2H)-one Chemical class C1=CC=C2C(=O)NC=CC2=C1 VDBNYAPERZTOOF-UHFFFAOYSA-N 0.000 description 1
- 229910052747 lanthanoid Inorganic materials 0.000 description 1
- 150000002602 lanthanoids Chemical group 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- LWLPYZUDBNFNAH-UHFFFAOYSA-M magnesium;butane;bromide Chemical compound [Mg+2].[Br-].CCC[CH2-] LWLPYZUDBNFNAH-UHFFFAOYSA-M 0.000 description 1
- LVKCSZQWLOVUGB-UHFFFAOYSA-M magnesium;propane;bromide Chemical compound [Mg+2].[Br-].C[CH-]C LVKCSZQWLOVUGB-UHFFFAOYSA-M 0.000 description 1
- UGVPKMAWLOMPRS-UHFFFAOYSA-M magnesium;propane;bromide Chemical compound [Mg+2].[Br-].CC[CH2-] UGVPKMAWLOMPRS-UHFFFAOYSA-M 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- WGLUNLJVYNJMBU-UHFFFAOYSA-N n-[2-(dimethylamino)ethyl]-n-[(3-methyl-1-oxo-2,4-dihydroisoquinolin-3-yl)methyl]decanamide Chemical compound C1=CC=C2C(=O)NC(CN(CCN(C)C)C(=O)CCCCCCCCC)(C)CC2=C1 WGLUNLJVYNJMBU-UHFFFAOYSA-N 0.000 description 1
- 229930014626 natural product Natural products 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
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 125000002734 organomagnesium group Chemical group 0.000 description 1
- ANRQGKOBLBYXFM-UHFFFAOYSA-M phenylmagnesium bromide Chemical group Br[Mg]C1=CC=CC=C1 ANRQGKOBLBYXFM-UHFFFAOYSA-M 0.000 description 1
- 238000004262 preparative liquid chromatography Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 229910052726 zirconium Inorganic materials 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The application belongs to the technical field of asymmetric catalytic synthesis, and particularly relates to a preparation method, a synthesis intermediate and catalytic application of a planar chiral indene metal complex with a benzoindene skeleton. The application provides a key intermediate- (R) -configuration, (S) -configuration chiral indenone for preparing the planar chiral indene metal complex and a chiral indene ligand without a coordinated side arm prepared based on the chiral indene ketone, wherein the chiral indene ligand has strong modifiable property and is easy to complex with a transition metal compound to prepare a single planar chiral indene metal complex, the planar chiral indene metal complex can be used as a catalyst for various asymmetric hydrocarbon activation reactions, and the chiral indene metal complex does not need to separate stereoisomers in the synthesis process, so that the synthesis difficulty and the cost in all aspects are greatly reduced.
Description
Technical Field
The application belongs to the technical field of asymmetric catalytic synthesis, and particularly relates to a preparation method, a synthesis intermediate and catalytic application of a planar chiral indene metal complex with a benzoindene skeleton.
Background
Asymmetric catalysis is an important method for synthesizing chiral organic molecules. The chiral indene metal catalyst is used as a catalyst with high reactivity and functional group compatibility, and is widely applied to asymmetric catalytic synthesis. The chiral indene ligand without the coordination side arm has great application value in asymmetric catalysis, wherein the chiral indene ligand without the coordination side arm refers to an indene ring without a coordination chiral substituent group, and a chiral framework on the indene ring can provide chiral control. The chiral indene ligand mainly based on chiral menthol skeleton reported in various documents can be complexed with zirconium, yttrium, cobalt and rhodium to form a metal catalyst. The catalyst has better catalytic effects in the asymmetric alkyl aluminizing reaction, the asymmetric hydroamination reaction of olefin, the asymmetric hydrogenation reaction and the like. In 2023, loginov problem group succeeded in synthesizing chiral indene ligand without coordination side arm by using natural product alpha-pinene as raw material, which is stereospecific when coordinated with rhodium, and chiral separation is not needed, but the structure is difficult to reform. The catalyst is applied to asymmetric hydrocarbon activation synthesis of chiral hydrogenated isoquinolinone. In recent years, progress has also been made in preparing planar chiral indene metal catalysts from achiral, non-coordinating side-arm indene ligands. The task group of Baik and Blakey in 2020 successfully resolved racemic rhodium complexes containing prochiral indene ligands by chiral preparative liquid chromatography to obtain optically pure chiral indene rhodium catalysts. The catalyst is successfully applied to asymmetric amidation reaction of allyl compounds and asymmetric aza cyclization of non-activated olefins.
Most indene ligands are not specific enough in stereoselectivity when being complexed with metal, stereoisomers can be generated, separation and purification are needed through chiral preparation liquid chromatography or recrystallization, operation is difficult, experimental cost is high, and synthesis of optical pure indene metal complex is difficult. Secondly, the existing chiral indene ligand without a coordinated side arm has poor modifiable property, and is difficult to obtain wide application in asymmetric catalysis and obtain excellent catalysis results. In addition, the existing chiral indene ligand without a coordination side arm has few types and the chiral indene ligand without the coordination side arm is very deficient.
Disclosure of Invention
Based on the above, the application develops a chiral indene ligand which has an easily-improved structure and can stereospecifically complex metal and has no coordination side arm, and a key intermediate (chiral indenone) for preparing the chiral indene ligand. Furthermore, the planar chiral indene metal complex prepared based on the chiral indene ligand has the performance of catalyzing asymmetric hydrocarbon activation reaction, and has excellent yield and enantioselectivity.
The first aspect of the present application provides a chiral indanone of (R) -configuration having a chemical structure as shown in formula (1), and of (S) -configuration having a chemical structure as shown in formula (2):
in a second aspect, the application discloses a method for synthesizing chiral indanone, the method comprising:
Step 1, performing condensation-reduction reaction on (R) -configuration, (S) -configuration or chiral ring aldol formed by (R) -configuration and (S) -configuration in any proportion and isopropyl malonate to generate (R) -configuration, (S) -configuration or ring aldonic acid formed by (R) -configuration and (S) -configuration in any proportion;
The chiral cyclic aldehyde of the (R) -configuration has a chemical structure shown in a formula (3), the chiral cyclic aldehyde of the (S) -configuration has a chemical structure shown in a formula (4), the cyclic propionic acid of the (R) -configuration has a chemical structure shown in a formula (5), and the cyclic propionic acid of the (S) -configuration has a chemical structure shown in a formula (6):
Step 2, the (S) -configuration, (R) -configuration or the cyclopropionic acid formed by the (S) -configuration and the (R) -configuration in any proportion is reacted in the methylsulfonic acid to respectively generate the chiral indenone formed by the (R) -configuration and the (S) -configuration in any proportion;
the chiral indenone in the (R) -configuration has a chemical structure shown in a formula (1), and the chiral indenone in the (S) -configuration has a chemical structure shown in a formula (2):
specifically, the synthesis method of the chiral indenone comprises the following steps: ① The chiral ring aldol formed by (R) -configuration and (S) -configuration in any proportion is reacted with isopropyl malonate, amine formate (the structural formula is R 4N+HCO2 -, wherein R is alkyl or hydrogen) or a mixture of amine and formic acid in a solvent to generate corresponding (R) -configuration, (S) -configuration or cyclopropionic acid formed by (R) -configuration and (S) -configuration in any proportion, wherein the solvent for the reaction can be DMF, DMSO, NMP, N, N-dimethylacetamide, acetone, acetonitrile, pyridine, ethyl acetate, N-diethylformamide, toluene, dioxane and other conventional solvents, and preferably the solvent is DMF; ② The (S) -configuration, (R) -configuration or the cyclopropionic acid formed by any proportion of the (S) -configuration and the (R) -configuration is reacted in the methanesulfonic acid to generate corresponding chiral indenone formed by any proportion of the (R) -configuration and the (S) -configuration.
In a third aspect, the present application provides a chiral indene ligand of (R) -configuration having a chemical structure as shown in formula (7), of (S) -configuration having a chemical structure as shown in formula (8), or of (R) -configuration and (S) -configuration in any ratio.
Wherein, in the formula (7) and the formula (8), R 1 is selected from alkyl, heteroalkyl, heteroaryl, or aryl; r 2 is selected from H, alkyl, heteroalkyl, heteroaryl, or aryl. Preferably, the R 1 is selected from Me、Et、iPr、iBu、tBu、Cy、Ph、2-Me-C6H4、2-OMe-C6H4、2-OEt-C6H4、2-OiPr-C6H4、2,6-di-OMe-C6H3 or 3,5-di- tBu-C6H3; the R 2 is selected from H, me, et, n Pr or Ph.
In a fourth aspect, the present application discloses a method for synthesizing the chiral indene ligand, the method comprising: reacting the chiral indenone with a nucleophile, and then dehydrating to prepare the chiral indene ligand.
In some embodiments, the nucleophile is selected from the group consisting of a grignard reagent RMgX, an organolithium reagent RLi, an organocopper reagent R 2 CuLi, an organozinc reagent R 2 Zn, or an organoaluminum R 3 Al reagent. Preferably, the nucleophile is MeMgBr、EtMgBr、iPrMgBr、iBuLi、tBuMgBr、CyMgBr、PhMgBr、2-Me-C6H4Li、2-OMe-C6H4Li、2-OEt-C6H4Li、2-OiPr-C6H4Li、2,6-di-OMe-C6H3Li or 3,5-di- tBu-C6H3 Li.
Specifically, the synthesis method of the chiral indene ligand further comprises the following steps: reacting the chiral indenone, the additive and a nucleophile, and then dehydrating to prepare the chiral indene ligand; the additive is lanthanide (III) salt, such as CeCl 3 or LnCl 3.2licl (ln=la, ce, nd), preferably, the additive is LaCl 3.2licl, which can improve the reaction yield.
In a fifth aspect, the present application provides a planar chiral indene metal complex having a benzindene skeleton, which has a chemical structure as shown in formula (9), and which has a chemical structure as shown in formula (10), and which has a (R) -configuration, a (S) -configuration, or a combination of the (R) -configuration and the (S) -configuration in any ratio:
Wherein, in the formula (9) and the formula (10), R 1 is selected from alkyl, heteroalkyl, heteroaryl, or aryl; r 2 is selected from H, alkyl, heteroalkyl, heteroaryl, or aryl; m is selected from rhodium, iridium, iron, cobalt, ruthenium, scandium, yttrium or lanthanum; l is selected from mono-olefin, diene, arene, halogen anion, acid radical anion, cyclopentadiene anion, indene anion, o-aminobenzyl anion, carbon monoxide, phosphine ligand, aza arene, amine compound or sulfur compound, n represents the number of ligand, n is an integer of 0-5; preferably, the R 1 is selected from Me、Et、iPr、iBu、tBu、Cy、Ph、2-Me-C6H4、2-OMe-C6H4、2-OEt-C6H4、2-OiPr-C6H4、2,6-di-OMe-C6H3 or 3,5-di- tBu-C6H3; the R 2 is selected from H, me, et, n Pr or Ph.
In a sixth aspect, the present application discloses a method for synthesizing the planar chiral indene metal complex, the method comprising: reacting the chiral indene ligand with a transition metal compound to generate a planar chiral indene metal complex, wherein L of the planar chiral indene metal complex is selected from mono-olefin or diene ligand, aromatic hydrocarbon, halogen anion, acid radical anion, cyclopentadiene anion, indene anion, o-aminobenzyl anion, carbon monoxide, phosphine ligand, aza-aromatic hydrocarbon, amine compound or sulfur compound, n represents the number of the ligand, and n is an integer of 0-5.
In a seventh aspect, the present application discloses a method for synthesizing the planar chiral indene metal complex, the method comprising:
step a, reacting the chiral indene ligand with a transition metal compound to generate a first planar chiral indene metal complex, wherein L of the first planar chiral indene metal complex is selected from mono-olefin or di-olefin ligands;
Step b, reacting the first planar chiral indene metal complex described in step a with an oxidizing agent, such as elemental halogen, a hydrogen halide, a peroxide or a metal oxidizing agent, to form a second planar chiral indene metal complex, wherein L of the second planar chiral indene metal complex is a halide anion, an acid radical anion, n represents the number of ligands, and n is an integer from 0 to 5, preferably the halide anion is selected from chlorine, bromine or iodine.
Specifically, the synthesis method of the planar chiral indene metal complex comprises the following steps: ① Heating and reacting a chiral indene ligand, a base reagent and a transition metal compound under solvent conditions to generate a first planar chiral indene metal complex, wherein the base reagent is an alkoxide (ROM, wherein R is alkyl, M is an alkali metal ion), an organolithium Reagent (RLi) or an organomagnesium reagent (RMgX), preferably the base reagent is KO t Bu; the solvent may be conventional solvents such as anhydrous tetrahydrofuran, anhydrous diethyl ether, dioxane, toluene, etc., preferably, tetrahydrofuran; ② Reacting the first planar chiral indene metal complex with an oxidant, such as elemental halogen (e.g., elemental iodine, chlorine, or elemental bromine), a hydrogen halide, a peroxide, or a metal oxidant, in the presence of a solvent to form a second planar chiral indene metal rhodium complex, preferably elemental iodine; the solvent used for the reaction may be a conventional solvent such as dehydrated ether, tetrahydrofuran, methylene chloride, 1, 2-dichloroethane, toluene, etc., and preferably the solvent is dehydrated ether.
In some embodiments, the transition metal compound is selected from rhodium compounds, iridium compounds, cobalt compounds, ruthenium compounds, scandium compounds, yttrium compounds, or lanthanum compounds. Preferably, the transition metal compound is a rhodium compound or an iridium compound; more preferably, the transition metal compound is [ Rh (COD) Cl ] 2.
The eighth aspect of the application discloses an application of the planar chiral indene metal complex or the planar chiral indene metal complex prepared by the synthesis method as a catalyst in catalyzing asymmetric hydrocarbon activation reaction.
Specifically, the asymmetric hydrocarbon activation reaction can be a reaction of N-BocO-benzamide and norbornene or cyclohexadiene to synthesize chiral dihydroisoquinolinone and a reaction of benzoic acid and alkyne to synthesize axial chiral isocoumarin.
The application provides a chiral indenone which is a key intermediate for preparing the planar chiral indene metal complex, a chiral indene ligand which is prepared based on the chiral indene ketone and has no coordination side arm, and the planar chiral indene metal complex prepared based on the chiral indene ligand. The chiral indene ligand provided by the application has strong modifiable property, is easy to complex with a transition metal compound to prepare a single plane chiral indene metal complex, can be used as a catalyst for various asymmetric hydrocarbon activation reactions, does not need to separate stereoisomers in the synthesis process of the chiral indene metal complex, and greatly reduces the synthesis difficulty and the cost in various aspects. The data of the embodiment of the application show that the planar chiral indene metal complex can catalyze asymmetric hydrocarbon activation reaction, and has excellent yield and enantioselectivity.
Drawings
In order to more clearly illustrate the embodiments of the present application or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below.
FIG. 1 is a synthetic route diagram of (R) -configured planar chiral indene metal complex-compounds (R) -5 and (R) -6 synthesized from (S) -configured chiral ring guaiac-compound (S) -1;
FIG. 2 is a synthetic route diagram of planar chiral indene metal complex-compounds (R) -5a and (R) -6a provided in the examples of the present application;
FIG. 3 is a synthetic route diagram of planar chiral indene metal rhodium complex-compounds (R) -5h and (R) -6h provided in the examples of the present application;
FIG. 4 is a synthetic route diagram of planar chiral indene metal rhodium complex-compounds (R) -5n and (R) -6n provided in the examples of the present application;
FIG. 5 is a synthetic route diagram of the planar chiral indene metal rhodium complex (compound (R) -6a to compound (R) -6 o) as a catalyst for catalyzing A1 and B1 to synthesize P1;
FIG. 6 is a synthetic route diagram of the planar chiral indene metal rhodium complex (compound (R) -6B) provided by the embodiment of the application as a catalyst for catalyzing A1 and B2 to synthesize P2;
FIG. 7 is a synthetic route diagram of the planar chiral indene metal rhodium complex (compound (R) -6 i) provided by the embodiment of the application as a catalyst for catalyzing A2 and B3 to synthesize P3.
Detailed Description
The application provides a preparation method, a synthesis intermediate and catalytic application of a planar chiral indene metal complex with a phenylindene skeleton, which are used for solving the technical defect that the number of the existing chiral indene ligand without a coordinated side arm is very small.
The following description of the technical solutions in the embodiments of the present application will be clear and complete, and it is obvious that the described embodiments are only some embodiments of the present application, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the application without making any inventive effort, are intended to be within the scope of the application.
Among them, the reagents or drugs used in the following examples are all commercially available or homemade.
FIG. 1 is a synthetic route diagram of a planar chiral indene metal complex of (R) -configuration synthesized from a chiral cyclic aldol of (S) -configuration, the synthetic method comprising: 1) The chiral ring guaiac ((S) -1) shown in the formula (4) reacts with isopropyl malonate to generate the ring guaiac ((S) -2) shown in the formula (6) by heating to 120 ℃ under the conditions of formic acid, triethylamine and DMF; 2) The cyclopropanoic acid ((S) -2) shown in the formula (6) reacts in methanesulfonic acid at 70 ℃ to generate chiral indenone ((R) -3 a) shown in the formula (11), wherein R in the formula (11) is H; then, the chiral indenone ((R) -3 a) shown in the formula (11) reacts with Cu (TFA) ·×H 2 O and K 2S2O8 in a solvent DMF at 100 ℃ to generate (R) -3b shown in the formula (12), and then the (R) -3b shown in the formula (12) reacts with hydrogen to generate chiral indenone ((R) -3 c) shown in the formula (13) under the catalysis of palladium carbon; 3) The chiral indenone ((R) -3 a) shown in the formula (11) or the chiral indenone ((R) -3 c) shown in the formula (13) respectively carry out addition reaction with a nucleophile (such as R 1 MgBr or R 1 Li), then hydrochloric acid is added for dehydration to obtain a chiral indenone ligand ((R) -4) shown in the formula (7), and the yield of the step can be improved by using an additive (such as LaCl 3.2LiCl); 4) Reacting the chiral indene ligand ((R) -4) shown in the formula (7) with a transition metal compound in KO t Bu and anhydrous tetrahydrofuran at 70 ℃ to generate a planar chiral indene metal complex ((R) -5) shown in the formula (14); then, the planar chiral indene metal complex ((R) -5) represented by formula (14) is reacted with halogen (e.g., iodine) in anhydrous diethyl ether at room temperature to produce the planar chiral indene metal complex ((R) -6) represented by formula (15).
Example 1
The embodiment provides a first method for synthesizing a planar chiral indene metal rhodium complex with a benzoindene skeleton, which specifically comprises the following steps:
As shown in fig. 2, taking the synthetic planar chiral indene metal rhodium complexes (R) -5a and (R) -6a as examples, the synthetic method comprises: ① The chiral ring aldol (compound (S) -1) and isopropyl malonate are condensed and reduced to generate compound (S) -2; ② Reacting the compound (S) -2 with methanesulfonic acid to generate chiral indenone (R) -3a; ③ Chiral indenone (R) -3a reacts with a nucleophilic reagent MeMgBr (other nucleophilic reagents are replaced for other examples) and is dehydrated by adding acid to generate chiral indene ligand (R) -4a; ④ The chiral indene ligand (R) -4a reacts with a transition metal compound [ Rh (COD) Cl ] 2 to generate a metal complex (R) -5a; ⑤ The metal complex (R) -5a reacts with iodine simple substance to generate the planar chiral indene metal rhodium complex (R) -6a.
The method comprises the following specific steps:
1. Synthesis of compound (S) -2: in a dry 100mL round bottom flask, chiral cyclic guaiac (S) -1 (5 g,21.1mmol,1.0 equiv), isopropyl malonate (3.6 g,25.3mmol,1.2 equiv), formic acid (2.5 mL), triethylamine (3.5 mL) and DMF (20 mL) were added at room temperature. The reaction solution was placed in an oil bath at 120℃and stirred for 24 hours. After the reaction solution was cooled to room temperature, water (60 mL) was added thereto, and extraction was performed with ethyl acetate (3X 30 mL). The organic phases were combined, washed with saturated brine (50 mL), dried over anhydrous sodium sulfate, and the filtrate was collected by filtration and concentrated by rotary evaporator. Purification of the crude product by silica gel column chromatography (PE/ea=3:1) gave compound (S) -2, which has the chemical formula:
The product is: compound (S) -2 is a white solid; 5.3g; the yield thereof was found to be 90%. Spec.rot.: δ＝6.71(dd,J＝7.9,1.9Hz,1H),6.54(dd,J＝7.9,1.9Hz,1H),6.51–6.38(m,4H),6.16(s,1H),3.43–3.30(m,1H),3.21–2.89(m,7H),2.88–2.79(m,1H),2.71–2.59(m,1H),2.58–2.44(m,2H).13C NMR(101MHz,CDCl3):δ＝179.3,140.2,139.6,139.5,139.4,137.6,135.1,134.3,133.5,133.3,132.2,131.0,128.9,35.4,35.1,34.8,34.3,33.5,29.1.HRMS(ESI)m/z:[M+H]+Calcd for C19H21O2281.1536;Found281.1543.
2. Synthesis of chiral indenone (compound (R) -3 a): in a dry 100mL round bottom flask, compound (S) -2 (1.0 g,3.5mmol,1.0 equiv) and methanesulfonic acid (20 g) were added at room temperature, and the reaction mixture was placed in an oil bath at 70℃and stirred for 12 hours. After the reaction solution was cooled to room temperature, it was poured into ice water (100 mL). Ethyl acetate extraction (3×10 mL). The organic phases were combined, washed with saturated brine (20 mL), dried over anhydrous sodium sulfate, and the filtrate was collected by filtration and concentrated by rotary evaporator. Purification of the crude product by silica gel column chromatography (PE/ea=6:1) gave compound (R) -3a, compound (R) -3a having the chemical formula:
The product is: compound (R) -3a is a white solid; 0.78g; the yield thereof was found to be 85%. Spec.rot.: δ＝6.66(d,J＝7.5Hz,1H),6.62–6.56(m,3H),6.45(dd,J＝7.8,2.0Hz,1H),6.30(dd,J＝7.9,2.0Hz,1H),4.25–4.13(m,1H),3.31–3.18(m,1H),3.17–3.02(m,4H),2.98–2.89(m,1H),2.89–2.69(m,3H),2.61–2.42(m,2H).13C NMR(101MHz,CDCl3):δ＝207.6,156.4,141.0,140.1,139.1,139.0,138.2,137.3,133.9,133.8,133.6,130.2,126.8,36.2,34.0,33.9,31.5,31.4,24.7.HRMS(ESI)m/z:[M+H]+Calcd for C19H19O 263.1430;Found 263.1436.
3. Synthesis of chiral indene ligand (compound (R) -4 a): in a dry 25mL round bottom flask, indenone (R) -3a (0.3 mmol,1.0 equiv), THF (2 mL) and LaCl 3.2 LiCl (0.6M in THF,1mL,2equiv) were added at room temperature under nitrogen and the reaction was stirred for 1 hour. After the reaction solution was cooled to 0 ℃, meMgBr (3 equiv) was slowly added thereto. The reaction was then continued at room temperature for 2 hours. After cooling the reaction to 0deg.C, 6M HCl (3 mL) was slowly added and the reaction was stirred for 1 hour. Extraction with ethyl acetate (3X 3 mL). The organic phases were combined, washed with saturated brine (3 mL), dried over anhydrous sodium sulfate, and the filtrate was collected by filtration and concentrated by rotary evaporator. Purifying the crude product by silica gel column chromatography (petroleum ether elution) to obtain a compound (R) -4a, wherein the chemical structural formula of the compound (R) -4a is as follows:
the product is: compound (R) -4a is a colorless liquid; 51mg; the yield thereof was found to be 65%. Spec.rot.: δ＝6.58(dd,J＝7.8,1.9Hz,1H),6.55–6.49(m,2H),6.43(d,J＝7.7Hz,1H),6.33(dd,J＝7.8,1.9Hz,1H),6.24(dd,J＝7.8,1.9Hz,1H),6.19–6.14(m,1H),3.72–3.57(m,1H),3.29–3.13(m,2H),3.12–2.96(m,3H),2.97–2.82(m,2H),2.81–2.68(m,2H),2.38–2.29(m,3H).13C NMR(101MHz,CDCl3):δ＝146.6,145.7,142.2,139.1,138.9,135.0,133.8,133.2,133.1,132.5,130.0,129.7,128.2,125.6,37.0,35.6,34.2,33.1,32.2,16.4.HRMS(APCI)m/z:[M+H]+Calcd for C20H21261.1638;Found 261.1639.
4. Synthesis of planar chiral indene metal rhodium complex 1-Compound (R) -5 a: after adding compound (R)-4a(0.25mmol,1.0equiv)、[Rh(COD)Cl]2(74mg,0.15mmol,0.6equiv)、KOtBu(42mg,0.375mmol,1.5equiv) and anhydrous tetrahydrofuran (2 mL) to a dry 25mL round bottom flask under nitrogen atmosphere at room temperature, the reaction mixture was placed in an oil bath at 70 ℃ and stirred for 20 hours. After cooling the reaction solution to room temperature, it was concentrated by a rotary evaporator. The crude product was purified by chromatography on an alkalinized silica gel column (5% triethylamine in petroleum ether) eluting with petroleum ether to give compound (R) -5a, compound (R) -5a having the formula:
the product is: compound (R) -5a is a yellow solid; 75mg; the yield thereof was found to be 83%. Spec.rot.: δ＝6.51–6.44(m,2H),6.35(d,J＝7.2Hz,1H),6.32(d,J＝7.2Hz,1H),6.26(dd,J＝7.7,1.7Hz,1H),6.01(dd,J＝7.7,1.7Hz,1H),5.78(t,J＝2.3Hz,1H),4.71(d,J＝2.8Hz,1H),3.64–3.55(m,2H),3.43–3.34(m,1H),3.27–3.17(m,2H),3.14–2.95(m,3H),2.94–2.79(m,3H),2.74–2.63(m,1H),1.99(s,3H),1.88–1.74(m,4H),1.69–1.57(m,4H).13C NMR(101MHz,CDCl3):δ＝138.2,138.1,131.9,131.8,131.6,131.0,129.6,128.1,127.5,127.4,115.9(d,J＝3.0Hz),115.4(d,J＝2.4Hz),92.9(d,J＝4.7Hz),88.9(d,J＝3.8Hz),74.6(d,J＝4.3Hz),70.1,70.0,66.8,66.7,36.0,34.6,33.9,33.0,31.6,31.4,13.4.HRMS(APCI)m/z:[M+H]+Calcd for C28H32Rh 471.1554;Found 471.1548.
5. Synthesis of planar chiral indene metal rhodium complex 2-Compound (R) -6 a: in a dry 25mL round bottom flask, compound (R) -5a (0.25 mmol,1.0 equiv), iodine (76 mg,0.3mmol,1.2 equiv) and anhydrous diethyl ether (5 mL) were added at room temperature and the reaction stirred for 1 hour. The resulting brown-black precipitate was collected by filtration with a buchner funnel and washed with diethyl ether (10 mL). Vacuum drying to obtain a compound (R) -6a, wherein the chemical structural formula of the compound (R) -6a is as follows:
The product is: compound (R) -6a is a brownish black solid, 59mg, yield 60％.1H NMR(400MHz,DMSO-d6:CDCl3(v/v＝1:1)):δ＝6.78(d,J＝7.3Hz,2H),6.69(d,J＝7.3Hz,2H),6.66–6.61(m,4H),6.38–6.24(m,2H),6.18–6.12(m,4H),5.99(d,J＝2.8Hz,2H),3.53–3.42(m,2H),3.33–3.02(m,12H),2.98–2.87(m,2H),2.42(s,6H).13C NMR(101MHz,DMSO-d6:CDCl3(v/v＝1:1)):δ＝139.9,139.1,139.0,138.9,137.3,136.4,133.0,132.5,131.3,130.6,113.1(d,J＝3.8Hz),111.3(d,J＝4.2Hz),97.3(d,J＝6.5Hz),91.8(d,J＝6.4Hz),73.5(d,J＝6.7Hz),35.3,34.3,33.5,33.1,14.1.HRMS(ESI)m/z:[M–I]+Calcd for C40H38I3Rh21104.8212;Found 110.48221.
Example 2
This example produces a planar chiral indene metal rhodium complex similar to example 1, and the method includes: the procedure was as in example 1, using chiral indanone (compound (R) -3 a) as starting material to prepare compound (R) -6b (chemical formula, below), wherein MeMgBr in step (R) -4a was replaced with EtMgBr (3 equiv), and the resulting compound (R) -6b was a tan solid; 79mg; yield is as follows 61％.HRMS(ESI)m/z:[M–I]+Calcd for C42H42I3Rh21132.8525;Found 1132.8536.
Example 3
This example produces a planar chiral indene metal rhodium complex similar to example 1, and the method includes: the procedure was as in example 1, using chiral indanone (compound (R) -3 a) as starting material to prepare compound (R) -6c (chemical formula, below), wherein MeMgBr in step (R) -4a was replaced with i PrMgBr (3 equiv), and the resulting compound (R) -6c was a tan solid; 87mg; yield is as follows 45％.HRMS(ESI)m/z:[M–I]+Calcd for C44H46I3Rh21160.8838;Found 1160.8844.
Example 4
This example produces a planar chiral indene metal rhodium complex similar to example 1, and the method includes: the procedure was as in example 1, using chiral indanone (compound (R) -3 a) as starting material to prepare compound (R) -6d (chemical formula, below), wherein MeMgBr in step (R) -4a was replaced with i BuLi (3 equiv), and compound (R) -6d was obtained as a tan solid; 86mg; yield is as follows 57％.HRMS(ESI)m/z:[M–I]+Calcd for C46H50I3Rh21188.9151;Found 1188.9159.
Example 5
This example produces a planar chiral indene metal rhodium complex similar to example 1, and the method includes: the procedure was as in example 1, using chiral indanone (compound (R) -3 a) as starting material to prepare compound (R) -6e (chemical formula, below), wherein MeMgBr in step (R) -4a was replaced with t BuMgBr (3 equiv), and compound (R) -6e was obtained as a tan solid; 45mg; yield is as follows 21％.HRMS(ESI)m/z:[M–I]+Calcd for C46H50I3Rh21188.9151;Found 1188.9145.
Example 6
This example produces a planar chiral indene metal rhodium complex similar to example 1, and the method includes: the procedure was as in example 1, using chiral indanone (compound (R) -3 a) as starting material to prepare compound (R) -6f (formula: below), wherein MeMgBr in step (R) -4a was replaced with CyMgBr (3 equiv), and the resulting compound (R) -6f was a tan solid; 78mg; yield is as follows 70％.HRMS(ESI)m/z:[M–I]+Calcd for C50H54I3Rh21240.9464;Found 1240.9472.
Example 7
This example produces a planar chiral indene metal rhodium complex similar to example 1, and the method includes: the procedure was as in example 1, except that chiral indanone (compound (R) -3 a) was used as starting material to prepare compound (R) -6g (chemical formula: below), wherein MeMgBr in step (R) -4a was replaced with PhMgBr (3 equiv), and the resulting compound (R) -6g was a brownish-black solid; 78mg; yield is as follows 70％.HRMS(ESI)m/z:[M–I]+Calcd for C50H54I3Rh21240.9464;Found 1240.9472.
Example 8
The present example provides a second class of methods for synthesizing planar chiral indene metal rhodium complexes having a phenylindene skeleton, comprising:
As shown in fig. 3, taking the synthetic planar chiral indene metal rhodium complexes (R) -5h and (R) -6h as examples, the synthetic method comprises: ① Reacting chiral indenone (R) -3a with nucleophilic reagent 2-methylbenzlithium (other nucleophilic reagent is used for other examples), and adding acid to dehydrate to generate chiral indene ligand (R) -4h; ② Reacting the chiral indene ligand (R) -4h with a transition metal compound [ Rh (COD) Cl ] 2 h to generate a compound (R) -5h; ③ The compound (R) -5h reacts with iodine simple substance to generate a planar chiral indene metal rhodium complex (R) -6h.
The method comprises the following specific steps:
1. Synthesis of Compound (R) -4 h: in a dry 25mL round bottom flask, chiral indanone (R) -3a (0.3 mmol,1.0 equiv) prepared in the above example, diethyl ether (2 mL) and LaCl 3. 2LiCl (0.6M inTHF,1mL,2equiv) were added at room temperature under nitrogen atmosphere and the reaction was stirred for 1 hour. In another dry 25mL round bottom flask, 2-bromotoluene (1 mmol,3.3 equiv), diethyl ether (2 mL) and n-butyllithium (2.5M inhexane,3equiv) were added under nitrogen at 0deg.C and the reaction was stirred for 1 hour. To the indenone reaction solution cooled to 0℃was slowly added the freshly prepared solution of 2-methylbenzlithium as described above, and the reaction was continued at room temperature for 2 hours. After cooling the reaction mixture to 0deg.C, 6M HCl (3 mL) was slowly added and the reaction was stirred for 1 hour. Followed by extraction with ethyl acetate (3X 3 mL). The organic phases were combined, washed with saturated brine (3 mL), dried over anhydrous sodium sulfate, and the filtrate was collected by filtration and concentrated by rotary evaporator. Purifying the crude product by silica gel column chromatography (petroleum ether elution) to obtain a compound (R) -4h, wherein the chemical structural formula of the compound (R) -4h is as follows:
The product is: compound (R) -4h is a white solid; 62mg; the yield thereof was found to be 61%. Spec.rot.: δ＝7.43(s,1H),7.34–7.13(m,3H),6.53–6.49(m,1H),6.48–6.44(m,1H),6.41–6.37(m,3H),6.33–6.29(m,1H),6.28–6.22(m,1H),3.28–3.14(m,2H),3.14–3.06(m,2H),3.05–2.98(m,1H),2.97–2.87(m,2H),2.70(dt,J＝12.7,6.2Hz,1H),2.52–2.43(m,2H),2.22–2.08(m,3H).13C NMR(101MHz,DMSO-d6,150℃):δ＝147.3,144.7,144.3,138.5,138.3,137.7,135.9,134.7,133.3,133.1,132.9,132.3,132.1,130.2,129.4,129.3,127.7,127.7,125.7,125.3,34.5,33.5,31.6,31.5,20.0.HRMS(APCI)m/z:[M+H]+Calcd for C26H25337.1951;Found 337.1943.
2. Synthesis of compound (R) -5 h: after adding compound (R)-4h(0.25mmol,1.0equiv)、[Rh(COD)Cl]2(74mg,0.15mmol,0.6equiv)、KOtBu(42mg,0.375mmol,1.5equiv) and anhydrous tetrahydrofuran (2 mL) to a dry 25mL round bottom flask under nitrogen atmosphere at room temperature, the reaction mixture was placed in an oil bath at 70 ℃ and stirred for 20 hours. After cooling the reaction solution to room temperature, it was concentrated by a rotary evaporator. The crude product was purified by chromatography on an alkalinized silica gel column (5% triethylamine in petroleum ether) (petroleum ether elution). Then, the reaction was carried out without further purification. The chemical structural formula of the compound (R) -5h is as follows:
3. Synthesis of planar chiral indene metal rhodium complex (Compound (R) -6 h): in a dry 25mL round bottom flask, the above-prepared compound (R) -5h (0.25 mmol,1.0 equiv), iodine (76 mg,0.3mmol,1.2 equiv) and dehydrated ether (5 mL) were added at room temperature, and the reaction was stirred for 1 hour. The resulting brown-black precipitate was collected by filtration with a buchner funnel and washed with diethyl ether (10 mL). Vacuum drying to obtain a compound (R) -6h, wherein the chemical structural formula of the compound (R) -6h is as follows:
The product is: compound (R) -6h is a tan solid; 56mg; yield is as follows 44％.1H NMR(400MHz,CDCl3:DMSO-d6(v/v＝1:1)):δ＝8.49(d,J＝7.8Hz,2H),7.46–7.33(m,4H),7.30–7.20(m,2H),6.82–6.61(m,8H),6.44–6.36(m,4H),6.29–6.20(m,2H),6.09–6.00(m,2H),3.38–3.20(m,4H),3.19–3.06(m,4H),2.89–2.72(m,6H),2.69(s,6H),2.18–2.05(m,2H).13C NMR(101MHz,CDCl3:DMSO-d6(v/v＝1:1)):δ＝141.8,141.5,138.8,138.7,135.6,135.0,134.9,133.4,132.9,131.9,131.0,130.9,130.4,129.5,129.2,125.5,119.0(d,J＝3.3Hz),102.4(d,J＝4.5Hz),94.3(d,J＝6.5Hz),93.1(d,J＝5.2Hz),78.9(d,J＝7.4Hz),34.8,34.4,33.3,33.2,21.0.HRMS(ESI)m/z:[M–I]+Calcd for C52H46I3Rh21256.8838;Found 1256.8835.
Example 9
This example produces a planar chiral indene metal rhodium complex similar to example 8, the method comprising: compound (R) -6i (chemical structural formula is shown below) was prepared using compound (R) -3a as a starting material by the same method as in example 8, wherein 2-bromotoluene in the (R) -4h synthesis step was replaced with 2-bromoanisole (3.3 equiv), and the resulting compound (R) -6i was a brownish black solid; 90mg; yield is as follows 74％.HRMS(ESI)m/z:[M–I]+Calcd for C52H46I3O2Rh21288.8736;Found 1288.8744.
Example 10
This example produces a planar chiral indene metal rhodium complex similar to example 8, the method comprising: compound (R) -6j (chemical structural formula is shown below) was prepared using compound (R) -3a as a starting material, and the synthesis method was the same as in example 8, wherein 2-bromotoluene in the (R) -4h synthesis step was replaced with 2-bromophenetole (3.3 equiv), and the obtained compound (R) -6j was a brownish black solid; 76mg; yield is as follows 83％.HRMS(ESI)m/z:[M–I]+Calcd for C54H50I3O2Rh21316.9049;Found 1316.9048.
Example 11
This example produces a planar chiral indene metal rhodium complex similar to example 8, the method comprising: the procedure was as in example 8, using compound (R) -3a as starting material to prepare compound (R) -6k (chemical formula: below), wherein 2-bromotoluene in the (R) -4h synthesis step was replaced with 1-bromo-2-isopropoxy benzene (3.3 equiv), and compound (R) -6k was obtained as a tan solid; 69mg; yield is as follows 77％.HRMS(ESI)m/z:[M–I]+Calcd for C56H54I3O2Rh21344.9362;Found 1344.9367.
Example 12
This example produces a planar chiral indene metal rhodium complex similar to example 8, the method comprising: the procedure was as in example 8, using compound (R) -3a as starting material to prepare compound (R) -6l (chemical formula: below), wherein 2-bromotoluene in the (R) -4h synthesis step was replaced with 1-bromo-2, 6-dimethoxybenzene (3.3 equiv), and compound (R) -6l was obtained as a tan solid; 26mg; yield is as follows 16％.HRMS(ESI)m/z:[M–I]+Calcd for C54H50I3O4Rh21348.8948;Found 1348.8956.
Example 13
This example produces a planar chiral indene metal rhodium complex similar to example 8, the method comprising: compound (R) -6m (chemical structural formula is shown below) was prepared using compound (R) -3a as a starting material, and the synthesis method was the same as in example 8, wherein 2-bromotoluene in the (R) -4h synthesis step was replaced with 3, 5-di-tert-butylbromobenzene (3.3 equiv), and the resulting compound (R) -6m was a brownish black solid; 57mg; yield is as follows 82％.HRMS(ESI)m/z:[M–I]+Calcd for C66H74I3Rh21453.1029;Found 1453.1020.
Example 14
The present example provides a third class of methods for synthesizing planar chiral indene metal rhodium complexes having a phenylindene skeleton, comprising:
As shown in fig. 4, taking the synthetic planar chiral indene metal rhodium complexes (R) -5n and (R) -6n as examples, the synthetic method comprises: ① Chiral indenone (R) -3a reacts with Cu (TFA) ×H 2 O and K 2S2O8 to generate compound (R) -3b; ② Reacting the compound (R) -3b with hydrogen to generate a compound (R) -3c under the catalysis of palladium-carbon; ③ Reacting the compound (R) -3c with a nucleophile EtMgBr (for other examples, other nucleophiles are replaced) and adding acid to dehydrate to generate chiral indene ligand (R) -4n; ④ The chiral indene ligand (R) -4n reacts with a transition metal compound [ Rh (COD) Cl ] 2 to generate a compound (R) -5n; ⑤ The compound (R) -5n reacts with iodine simple substance to generate the planar chiral indene metal rhodium complex (R) -6n.
The method comprises the following specific steps:
1. Synthesis of compound (R) -3 b: after adding compound (R)-3a(100mg,0.38mmol,1.0equiv)、Cu(TFA)·×H2O(120mg,0.38mmol,1equiv)、K2S2O8(205mg,0.76mmol,2equiv) and anhydrous DMF (5 mL) in a dry 25mL round bottom flask under nitrogen at room temperature, the reaction was stirred in an oil bath at 100deg.C for 24 hours. After the reaction solution was cooled to room temperature, pure water (25 mL) was slowly added to the reaction solution. Extraction with ethyl acetate (3X 5 mL). The organic phases were combined, washed with saturated brine (10 mL), dried over anhydrous sodium sulfate, and the filtrate was collected by filtration and concentrated by rotary evaporator. Purification of the crude product by silica gel column chromatography (PE/ea=8:1) gives compound (R) -3b, which has the following chemical formula:
The product is: compound (R) -3b is a white solid; 74mg; yield 71%. Spec. δ＝6.68(d,J＝7.6Hz,1H),6.63–6.58(m,2H),6.53(dd,J＝7.9,2.0Hz,1H),6.45(dd,J＝7.8,2.0Hz,1H),6.30–6.27(m,1H),6.25(dd,J＝7.9,2.0Hz,1H),5.65–5.58(m,1H),4.40–4.25(m,1H),3.54–3.33(m,2H),3.26–3.17(m,1H),3.16–3.05(m,4H),3.02–2.91(m,1H),2.91–2.79(m,1H).13C NMR(101MHz,CDCl3):δ＝194.2,150.9,143.5,141.7,140.1,139.4,139.3,139.0,136.9,134.3,133.7,133.5,130.4,126.9,118.5,34.0,33.9,31.6,31.0.HRMS(ESI)m/z:[M+H]+Calcd for C20H19O275.1430;Found 275.1436.
2. Synthesis of compound (R) -3 c: in a dry 25mL round bottom flask, after addition of compound (R) -3b (74 mg,0.27mmol,1.0 equiv), pd/C (10% w/w,0.05 equiv) and ethyl acetate (3 mL) at room temperature, the reaction atmosphere was replaced with hydrogen and one hydrogen balloon was attached. The reaction solution was then placed in an oil bath at 60℃and stirred for reaction for 6 hours. The reaction solution was cooled to room temperature, filtered, and concentrated by rotary evaporator. The crude product was purified by column chromatography on silica gel (PE/ea=8:1) to give compound (R) -3c, which has the following chemical formula:
The product is: compound (R) -3c is a white solid; 72mg; yield 96%. Spec. δ＝6.65(d,J＝7.5Hz,1H),6.62–6.54(m,3H),6.46(dd,J＝7.9,2.0Hz,1H),6.21(dd,J＝8.0,1.9Hz,1H),4.29–4.13(m,1H),3.23–3.02(m,6H),2.99–2.89(m,1H),2.87–2.78(m,1H),2.52–2.33(m,2H),1.40(d,J＝7.2Hz,3H).13C NMR(101MHz,CDCl3):δ＝209.5,153.9,141.0,140.2,139.1,139.0,137.2,137.1,133.9,133.7,133.3,130.7,127.1,41.5,34.1,33.9,31.5,31.3,15.2.HRMS(ESI)m/z:[M+H]+Calcd for C20H21O 277.1587;Found 277.1594.
3. Synthesis of chiral indene ligand (compound (R) -4 n): in a dry 25mL round bottom flask, indenone (R) -3c (0.3 mmol,1.0 equiv) THF (2 mL) and LaCl 3.2 LiCl (0.6M in THF,1mL,2equiv) were added at room temperature under nitrogen and the reaction was stirred for 1 hour. After the reaction solution was cooled to 0 ℃, ethyl magnesium bromide (3 equiv) was slowly added thereto. After the reaction was continued at room temperature for 2 hours, the reaction solution was cooled to 0℃and 6M HCl (3 mL) was slowly added thereto, and the reaction was stirred for 1 hour. Ethyl acetate extraction (3×3 mL). The combined organic phases were washed with saturated brine (3 mL), dried over anhydrous sodium sulfate, and the filtrate was collected by filtration and concentrated on a rotary evaporator. Purifying the crude product by silica gel column chromatography (petroleum ether elution) to obtain a compound (R) -4n, wherein the chemical structural formula of the compound (R) -4n is as follows:
The product is: compound (R) -4n is a colorless liquid; 75mg; yield 87%. Spec. δ＝6.60–6.50(m,2H),6.43(d,J＝7.7Hz,1H),6.36–6.28(m,2H),6.22–6.15(m,1H),3.54–3.38(m,1H),3.20–3.05(m,2H),3.05–2.97(m,2H),2.97–2.80(m,3H),2.78–2.63(m,3H),2.54–2.41(m,1H),2.09(s,3H),1.10(t,J＝7.6Hz,3H).13C NMR(101MHz,CDCl3):δ＝146.3,143.3,141.3,139.1,138.8,137.6,134.3,134.0,133.0,132.5,131.8,129.0,128.2,125.5,42.3,35.7,34.2,33.6,32.2,19.9,14.04,13.95.HRMS(APCI)m/z:[M+H]+Calcd for C22H25289.1951;Found 289.1947.
4. Synthesis of compound (R) -5 n: after adding chiral indene ligand (compound (R)-4n)(0.25mmol,1.0equiv)、[Rh(COD)Cl]2(74mg,0.15mmol,0.6equiv)、KOtBu(42mg,0.375mmol,1.5equiv) and anhydrous tetrahydrofuran (2 mL) to a dry 25mL round bottom flask under nitrogen atmosphere and at room temperature, the reaction mixture was stirred in an oil bath at 70 ℃ for 20 hours, the reaction mixture was cooled to room temperature and concentrated by a rotary evaporator, and the crude product was purified by chromatography on an alkalinized silica gel column (5% triethylamine in petroleum ether) (elution with petroleum ether) to give compound (R) -5n having the following chemical formula:
The product is: compound (R) -5n is a yellow solid; 86mg; yield 66%. Spec. δ＝6.58–6.48(m,2H),6.32–6.21(m,2H),6.15–6.07(m,2H),4.93(d,J＝4.2Hz,1H),3.67–3.33(m,3H),3.15–3.01(m,2H),2.99–2.87(m,6H),2.82–2.70(m,1H),2.62–2.43(m,1H),2.36–2.22(m,4H),1.98–1.74(m,4H),1.70–1.56(m,4H),1.51–1.41(m,3H).13C NMR(101MHz,CDCl3):δ＝138.6,138.3,131.9,131.8,131.5,131.1,128.6,127.8,127.6,115.0,110.9(d,J＝2.2Hz),106.2(d,J＝4.7Hz),94.8(d,J＝3.1Hz),78.0(d,J＝4.2Hz),71.4,71.3,67.7,67.6,35.2,34.5,33.3,33.2,32.0,31.4,20.1,15.3,13.1.HRMS(APCI)m/z:[M+H]+Calcd for C30H36Rh 499.1867;Found 499.1863.
4. Synthesis of compound (R) -6 n: in a dry 25mL round bottom flask, compound (R) -5n (0.25 mmol,1.0 equiv), iodine (76 mg,0.3mmol,1.2 equiv) and anhydrous diethyl ether (5 mL) were added at room temperature and the reaction stirred for 1 hour. The resulting brown-black precipitate was collected by filtration with a buchner funnel, washed with diethyl ether (10 mL), and dried in vacuo to give compound (R) -6n having the following chemical formula:
The product is: compound (R) -6n is a tan solid; 85mg; yield is as follows 77％.1H NMR(400MHz,DMSO-d6:CDCl3(v/v＝1:1)):δ＝6.79(d,J＝7.2Hz,2H),6.76–6.68(m,4H),6.66(d,J＝7.2Hz,2H),6.25(dd,J＝7.9,1.8Hz,2H),6.16(dd,J＝7.7,1.8Hz,2H),5.79(s,2H),3.45–3.35(m,2H),3.30–3.17(m,6H),3.14–3.02(m,6H),2.99–2.85(m,4H),2.67(s,6H),2.65–2.60(m,2H),1.54(t,J＝7.6Hz,6H).13C NMR(101MHz,DMSO-d6:CDCl3(v/v＝1:1)):δ＝140.4,139.7,139.3,138.8,136.4,135.6,132.8,132.5,131.5,129.9,115.0(d,J＝5.1Hz),114.5(d,J＝6.1Hz),104.3(d,J＝5.3Hz),91.8(d,J＝6.1Hz),75.4(d,J＝6.7Hz),35.0,34.3,33.5,32.7,20.5,15.0,13.5.HRMS(ESI)m/z:[M–I]+Calcd for C44H46I3Rh21160.8838;Found 1160.8843.
Example 15
This example prepares a planar chiral indene metal rhodium complex similar to example 14, the method comprising: compound (R) -6o (chemical structural formula is shown below) was prepared using compound (R) -3c prepared in example 14 as a starting material, and was synthesized in the same manner as in example 14, wherein ethylmagnesium bromide in the (R) -4n synthesis step was replaced with phenylmagnesium bromide (3 equiv), and the resulting compound (R) -6o was a brownish-black solid; 106mg; yield is as follows 76％.HRMS(ESI)m/z:[M–I]+Calcd for C52H46I3Rh21256.8838;Found1256.8830.
Example 16
This example uses the 15 planar chiral indene metal rhodium complexes (compounds (R) -6a through (R) -6 o) prepared in the above example as catalysts for asymmetric hydrocarbon activation reactions, and the test experiments are as follows:
FIG. 5 shows the planar chiral indene metal rhodium complexes (compounds (R) -6a to (R) -6 o) prepared in examples 1 to 15 as catalysts for catalyzing the synthesis of P1 from A1 and B1, comprising the following steps:
After adding compound A1 (0.05 mmol,1.0 equiv), B1 (0.075 mmol,1.5 equiv), catalyst (compound (R) -6a,1.3mg,0.001mmol,2 mol%), agOAc (1.7 mg,0.01mmol,20 mol%), csOAc (2.5 mg,0.025mmol,50 mol%) and anhydrous methanol (0.25 mL) to a dry 15mL pressure-resistant tube at room temperature, stirring was carried out at room temperature for 16 hours. And then concentrated using a rotary evaporator. The crude product was purified by column chromatography on silica gel (PE/ea=2:1) to give product P1. The ee value of the product was determined by HPLC.
Catalytic results for catalyst (R) -6 a: product P1 was a white solid; 7.1mg; the yield thereof was found to be 67%, and the ee value thereof was found to be 75%. HPLC (high Performance liquid chromatography)IA/>2-Propanol/n-hexane =20/80,flow rate 1.0mL/min, column temp.30 ℃, detection at 254nm, retention time of 7.1min (large peak) and 12.4min (small peak) ).1H NMR(400MHz,CDCl3):δ＝8.08(dd,J＝7.9,1.5Hz,1H),7.42(td,J＝7.5,1.5Hz,1H),7.29–7.22(m,1H),7.19(d,J＝7.7Hz,1H),6.96(s,1H),3.79(d,J＝8.9Hz,1H),3.09(d,J＝8.9Hz,1H),2.31–2.27(m,1H),2.27–2.25(m,1H),1.69–1.55(m,3H),1.55–1.47(m,1H),1.39–1.27(m,1H),1.18–1.11(m,1H).
Other catalysts (compound (R) -6B to compound (R) -6 o) were used for the reaction of compound A1 with compound B1 according to the methods described above. The yield and ee value of the product P1 are shown in Table 1 below.
Table 1 experimental results
Example 17
In this example, the planar chiral indene metal rhodium complex (compound (R) -6 b) prepared in the above example was used as a catalyst for asymmetric hydrocarbon activation, and the test experiment was as follows:
FIG. 6 shows a planar chiral indene metal rhodium complex (compound (R) -6B) as a catalyst for catalyzing the reaction of A1 and B2 to synthesize P2, comprising the following steps:
after adding compound A1 (0.1 mmol,1.0 equiv), B2 (0.15 mmol,1.5 equiv), catalyst (R) -6B (2.5 mg,0.002mmol,2 mol%), agOAc (8 mol%), csOAc (5 mg,0.05mmol,50 mol%) and anhydrous methanol (0.5 mL) at room temperature in a dry 15mL pressure-resistant tube with a threaded port, stirring was performed at zero℃for 24 hours. And then concentrated using a rotary evaporator. The crude product was purified by column chromatography on silica gel (PE/ea=2:1) to give product P2. The ee value of the product was determined by HPLC.
Catalytic results for catalyst (R) -6 b: product P2 was a white solid; 19.1mg; the yield was 96%, ee.% and 97%. Spec.rot.: 2-propanol/n-hexane =20/80,flow rate 1.0mL/min, column temp.30 ℃, detection at 254nm, retention time 18.5min (large peak) and 20.1min (small peak) ).1H NMR(400MHz,CDCl3):δ＝8.07(dd,J＝7.7,1.4Hz,1H),7.49(td,J＝7.5,1.4Hz,1H),7.36(td,J＝7.6,1.3Hz,1H),7.28–7.20(m,1H),6.26–5.95(m,1H),5.91–5.71(m,2H),4.28(t,J＝4.9Hz,1H),2.94(dt,J＝12.3,4.0Hz,1H),2.38–2.16(m,2H),2.07–1.89(m,1H),1.75–1.64(m,1H).
Example 18
In this example, the planar chiral indene metal rhodium complex (compound (R) -6 i) prepared in the above example is used as a catalyst for asymmetric hydrocarbon activation reaction, and the test experiment is as follows:
as shown in fig. 7, fig. 7 shows a planar chiral indene metal rhodium complex (compound (R) -6 i) as a catalyst for catalyzing the reaction of A2 and B3 to synthesize P3, and the specific steps include:
In a dry 15mL pressure-resistant tube with a threaded port, benzoic acid A2 (0.1 mmol,1.0 equiv), alkyne B3 (0.12 mmol,1.2 equiv), catalyst (R) -6i (0.005 mmol,5 mol%), agOPiv (4.2 mg,0.02mmol,20 mol%), cu (OPiv) 2 (26.6 mg,0.1mmol,1 equiv) and trifluoroethanol (0.5 mL) were added at room temperature and stirred at room temperature for 20 hours. And then concentrated using a rotary evaporator. The crude product was purified by column chromatography on silica gel (PE/ea=8:1) to give product P3. The ee value of the product was determined by HPLC.
Catalytic results for catalyst (R) -6 i: product P3 was a white solid, 47.4mg, yield 98%, ee. value 94%. HPLC (high Performance liquid chromatography)IF column (n-hexane/i-PrOH=85:15, 1.0mL/min, λ=254 nm), retention time 15.4min (small peak) and 31.2min (large peak) Spec. Rot.).δ＝8.49–8.42(m,1H),7.90(d,J＝8.6Hz,1H),7.87–7.81(m,1H),7.59–7.51(m,1H),7.51–7.42(m,2H),7.38–7.29(m,5H),7.21–7.13(m,1H),7.12–7.02(m,2H),6.93–6.82(m,2H),6.78–6.72(m,1H),6.72–6.65(m,2H),4.97(d,J＝12.2Hz,1H),4.89(d,J＝12.2Hz,1H),3.75(s,3H).13C NMR(101MHz,CDCl3):δ＝162.8,159.2,154.4,152.2,139.1,134.7,134.1,133.3,130.5,129.5,129.1,129.1,128.9,128.4,128.4,128.1,128.0,127.9,127.4,125.4,124.6,124.1,120.6,117.1,115.1,113.8,110.8,70.4,55.2.HRMS(ESI)m/z:[M+H]+Calcd for C33H25O4485.1747;Found 485.1743.
In summary, the embodiment of the application provides a synthetic intermediate (chiral indenone) of a chiral indene ligand without a coordinating side arm, which has an easily-modified structure and can stereospecifically complex metal. The chiral indene ligand in the application has strong modifiable property, is easy to synthesize a plurality of chiral indene ligands without coordinating side arms, can be constructed to obtain a chiral indene ligand library with rich structure, and can meet the requirements of different reactions on different chiral environments of the catalyst. In addition, the application utilizes the steric hindrance control of the chiral indene ligand, and a single plane chiral indene metal complex is obtained when the transition metal compound is complexed with the chiral indene ligand, so that a stereoisomer is not required to be separated, the synthesis difficulty and the cost in all aspects are greatly reduced, the catalytic performance is displayed in three asymmetric hydrocarbon activation reactions, and the method has excellent yield and enantioselectivity.
The foregoing is merely a preferred embodiment of the present application and it should be noted that modifications and adaptations to those skilled in the art may be made without departing from the principles of the present application, which are intended to be comprehended within the scope of the present application.
Claims (10)
1. A chiral indanone of (R) -configuration having a chemical structure as shown in formula (1), and a chiral indanone of (S) -configuration having a chemical structure as shown in formula (2):
2. A method of synthesizing a chiral indanone, the method comprising:
Step 1, performing condensation-reduction reaction on (R) -configuration, (S) -configuration or chiral ring aldol formed by (R) -configuration and (S) -configuration in any proportion and isopropyl malonate to generate (R) -configuration, (S) -configuration or ring aldonic acid formed by (R) -configuration and (S) -configuration in any proportion;
The chiral cyclic aldehyde of the (R) -configuration has a chemical structure shown in a formula (3), the chiral cyclic aldehyde of the (S) -configuration has a chemical structure shown in a formula (4), the cyclic propionic acid of the (R) -configuration has a chemical structure shown in a formula (5), and the cyclic propionic acid of the (S) -configuration has a chemical structure shown in a formula (6):
Step 2, the (S) -configuration, (R) -configuration or the cyclopropionic acid formed by the (S) -configuration and the (R) -configuration in any proportion is reacted in the methylsulfonic acid to respectively generate the chiral indenone formed by the (R) -configuration and the (S) -configuration in any proportion;
the chiral indenone in the (R) -configuration has a chemical structure shown in a formula (1), and the chiral indenone in the (S) -configuration has a chemical structure shown in a formula (2):
3. a chiral indene ligand of (R) -configuration having a chemical structure as shown in formula (7), a (S) -configuration having a chemical structure as shown in formula (8), or a chiral indene ligand of (R) -configuration and (S) -configuration in any ratio.
Wherein, in the formula (7) and the formula (8), R 1 is selected from alkyl, heteroalkyl, heteroaryl, or aryl; r 2 is selected from H, alkyl, heteroalkyl, heteroaryl, or aryl.
4. A method of synthesizing the chiral indene ligand of claim 3, the method comprising: reacting the chiral indenone of claim 1 with a nucleophile, followed by dehydration to produce a chiral indene ligand.
5. The method of claim 4, wherein the nucleophile is selected from the group consisting of a grignard reagent, an organolithium nucleophile, an organocopper nucleophile, an organozinc nucleophile, and an organoaluminum nucleophile.
6. A (R) -configuration, a (S) -configuration, or a planar chiral indene metal complex having a benzindene skeleton constituted by any ratio of the (R) -configuration to the (S) -configuration, the (R) -configuration planar chiral indene metal complex having a chemical structure as shown in formula (9), the (S) -configuration planar chiral indene metal complex having a chemical structure as shown in formula (10):
Wherein, in the formula (9) and the formula (10), R 1 is selected from alkyl, heteroalkyl, heteroaryl, or aryl; r 2 is selected from H, alkyl, heteroalkyl, heteroaryl, or aryl; m is selected from rhodium, iridium, iron, cobalt, ruthenium, scandium, yttrium or lanthanum; l is selected from mono-olefin, diene, arene, halogen anion, acid radical anion, cyclopentadiene anion, indene anion, o-aminobenzyl anion, carbon monoxide, phosphine ligand, aza arene, amine compound or sulfur compound, n represents the number of ligand, n is an integer of 0-5.
7. A method of synthesizing the planar chiral indene metal complex of claim 6, the method comprising: reacting the chiral indene ligand of claim 3 with a transition metal compound to form a planar chiral indene metal complex, wherein L of the planar chiral indene metal complex is selected from the group consisting of mono-or di-olefin ligands, aromatic hydrocarbons, halide anions, acid radical anions, cyclopentadiene anions, indene anions, anthranilate anions, carbon monoxide, phosphine ligands, aza-aromatic hydrocarbons, amine compounds, or sulfur compounds, n represents the number of ligands, and n is an integer from 0 to 5.
8. A method of synthesizing the planar chiral indene metal complex of claim 6, the method comprising:
Step a, reacting the chiral indene ligand of claim 3 with a transition metal compound to form a first planar chiral indene metal complex, wherein L of the first planar chiral indene metal complex is selected from a mono-olefin or a di-olefin ligand;
Step b, reacting the first planar chiral indene metal complex in the step a with an oxidant, such as elemental halogen, hydrogen halide, peroxide or metal oxidant, to generate a second planar chiral indene metal complex, wherein L of the second planar chiral indene metal complex is halogen anions and acid radical anions, n represents the number of ligands, and n is an integer of 0-5.
9. The method of claim 7 or 8, the transition metal compound being selected from rhodium compounds, iridium compounds, iron compounds, cobalt compounds, ruthenium compounds, scandium compounds, yttrium compounds, or lanthanum compounds.
10. Use of a planar chiral indene metal complex of claim 6 or prepared by a method of any of claims 7 to 9 as a catalyst in catalyzing asymmetric hydrocarbon activation reactions.
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