JP2019504041A - キラルスピロビインダン骨格化合物及びその製造方法 - Google Patents
キラルスピロビインダン骨格化合物及びその製造方法 Download PDFInfo
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- JP2019504041A JP2019504041A JP2018533768A JP2018533768A JP2019504041A JP 2019504041 A JP2019504041 A JP 2019504041A JP 2018533768 A JP2018533768 A JP 2018533768A JP 2018533768 A JP2018533768 A JP 2018533768A JP 2019504041 A JP2019504041 A JP 2019504041A
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- -1 spirobiindane skeleton compound Chemical class 0.000 title claims abstract description 58
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 56
- 150000001875 compounds Chemical class 0.000 claims abstract description 179
- 239000002904 solvent Substances 0.000 claims abstract description 115
- 238000006243 chemical reaction Methods 0.000 claims abstract description 67
- 239000003054 catalyst Substances 0.000 claims abstract description 56
- 238000000034 method Methods 0.000 claims abstract description 47
- 238000006898 Intramolecular Friedel-Crafts reaction Methods 0.000 claims abstract description 21
- 230000009471 action Effects 0.000 claims abstract description 19
- 230000003197 catalytic effect Effects 0.000 claims abstract description 10
- 229910052740 iodine Inorganic materials 0.000 claims abstract description 7
- 239000007848 Bronsted acid Substances 0.000 claims abstract description 5
- 229910052723 transition metal Inorganic materials 0.000 claims abstract description 5
- 150000003624 transition metals Chemical class 0.000 claims abstract description 5
- 125000003118 aryl group Chemical group 0.000 claims description 65
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 46
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 31
- 238000009876 asymmetric hydrogenation reaction Methods 0.000 claims description 31
- 239000003446 ligand Substances 0.000 claims description 26
- 238000006467 substitution reaction Methods 0.000 claims description 25
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 22
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 22
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 21
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims description 21
- 239000007789 gas Substances 0.000 claims description 19
- 239000003513 alkali Substances 0.000 claims description 16
- 238000005882 aldol condensation reaction Methods 0.000 claims description 14
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 13
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 13
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 10
- 229910052799 carbon Inorganic materials 0.000 claims description 10
- 125000004432 carbon atom Chemical group C* 0.000 claims description 10
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 9
- 125000006736 (C6-C20) aryl group Chemical group 0.000 claims description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 9
- 125000001624 naphthyl group Chemical group 0.000 claims description 9
- 230000035484 reaction time Effects 0.000 claims description 9
- 239000002841 Lewis acid Substances 0.000 claims description 8
- 150000004945 aromatic hydrocarbons Chemical class 0.000 claims description 8
- 150000008282 halocarbons Chemical class 0.000 claims description 8
- 150000007517 lewis acids Chemical class 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- 150000008300 phosphoramidites Chemical class 0.000 claims description 8
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 7
- 239000000460 chlorine Substances 0.000 claims description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 7
- 230000001681 protective effect Effects 0.000 claims description 7
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 6
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 150000001408 amides Chemical class 0.000 claims description 6
- 150000001721 carbon Chemical group 0.000 claims description 6
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 6
- 150000002431 hydrogen Chemical class 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 229910052741 iridium Inorganic materials 0.000 claims description 6
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 claims description 6
- 238000002156 mixing Methods 0.000 claims description 6
- 150000003462 sulfoxides Chemical class 0.000 claims description 6
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 5
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 5
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 5
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 5
- 229910052794 bromium Inorganic materials 0.000 claims description 5
- 229910052801 chlorine Inorganic materials 0.000 claims description 5
- 229910052731 fluorine Inorganic materials 0.000 claims description 5
- 239000011737 fluorine Substances 0.000 claims description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
- 239000011630 iodine Substances 0.000 claims description 5
- 229920006395 saturated elastomer Polymers 0.000 claims description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 claims description 4
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 229920000137 polyphosphoric acid Polymers 0.000 claims description 4
- 239000010948 rhodium Substances 0.000 claims description 4
- HZXJVDYQRYYYOR-UHFFFAOYSA-K scandium(iii) trifluoromethanesulfonate Chemical compound [Sc+3].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F HZXJVDYQRYYYOR-UHFFFAOYSA-K 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- VXUYXOFXAQZZMF-UHFFFAOYSA-N titanium(IV) isopropoxide Chemical compound CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C VXUYXOFXAQZZMF-UHFFFAOYSA-N 0.000 claims description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 4
- 238000001816 cooling Methods 0.000 claims description 3
- 239000004210 ether based solvent Substances 0.000 claims description 3
- 229940098779 methanesulfonic acid Drugs 0.000 claims description 3
- 239000012046 mixed solvent Substances 0.000 claims description 3
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 3
- IYDGMDWEHDFVQI-UHFFFAOYSA-N phosphoric acid;trioxotungsten Chemical compound O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.OP(O)(O)=O IYDGMDWEHDFVQI-UHFFFAOYSA-N 0.000 claims description 3
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 claims description 3
- 229910015900 BF3 Inorganic materials 0.000 claims description 2
- 238000005727 Friedel-Crafts reaction Methods 0.000 claims description 2
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 claims description 2
- 229910021627 Tin(IV) chloride Inorganic materials 0.000 claims description 2
- 150000001335 aliphatic alkanes Chemical class 0.000 claims description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims description 2
- UCYRAEIHXSVXPV-UHFFFAOYSA-K bis(trifluoromethylsulfonyloxy)indiganyl trifluoromethanesulfonate Chemical compound [In+3].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F UCYRAEIHXSVXPV-UHFFFAOYSA-K 0.000 claims description 2
- 150000004696 coordination complex Chemical class 0.000 claims description 2
- SBTSVTLGWRLWOD-UHFFFAOYSA-L copper(ii) triflate Chemical compound [Cu+2].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F SBTSVTLGWRLWOD-UHFFFAOYSA-L 0.000 claims description 2
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 claims description 2
- 229910052760 oxygen Inorganic materials 0.000 claims description 2
- 229910052763 palladium Inorganic materials 0.000 claims description 2
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 2
- USPWKWBDZOARPV-UHFFFAOYSA-N pyrazolidine Chemical compound C1CNNC1 USPWKWBDZOARPV-UHFFFAOYSA-N 0.000 claims description 2
- 229910052703 rhodium Inorganic materials 0.000 claims description 2
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 claims description 2
- 229910052707 ruthenium Inorganic materials 0.000 claims description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 claims description 2
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 claims description 2
- 239000007858 starting material Substances 0.000 abstract description 8
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 7
- 230000003287 optical effect Effects 0.000 abstract description 6
- 239000000126 substance Substances 0.000 abstract description 5
- 239000011968 lewis acid catalyst Substances 0.000 abstract 1
- 238000010626 work up procedure Methods 0.000 abstract 1
- 238000005481 NMR spectroscopy Methods 0.000 description 111
- 239000000047 product Substances 0.000 description 97
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 55
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 54
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 44
- 239000007787 solid Substances 0.000 description 43
- 238000004128 high performance liquid chromatography Methods 0.000 description 38
- 239000000758 substrate Substances 0.000 description 36
- 238000001514 detection method Methods 0.000 description 33
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical group CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
- 239000012071 phase Substances 0.000 description 30
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 27
- 238000002474 experimental method Methods 0.000 description 27
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 24
- 238000007363 ring formation reaction Methods 0.000 description 24
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
- 238000012512 characterization method Methods 0.000 description 18
- 239000003480 eluent Substances 0.000 description 17
- 239000007788 liquid Substances 0.000 description 17
- 239000003208 petroleum Substances 0.000 description 15
- 150000001340 alkali metals Chemical class 0.000 description 14
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 229910052783 alkali metal Inorganic materials 0.000 description 12
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 12
- 229910052786 argon Inorganic materials 0.000 description 12
- 238000004440 column chromatography Methods 0.000 description 11
- 238000005984 hydrogenation reaction Methods 0.000 description 11
- 239000000203 mixture Substances 0.000 description 11
- OPELWUSJOIBVJS-UHFFFAOYSA-N 3,3'-spirobi[1,2-dihydroindene] Chemical group C12=CC=CC=C2CCC11C2=CC=CC=C2CC1 OPELWUSJOIBVJS-UHFFFAOYSA-N 0.000 description 10
- 238000002451 electron ionisation mass spectrometry Methods 0.000 description 10
- 238000003756 stirring Methods 0.000 description 9
- 239000012298 atmosphere Substances 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
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- 229910002027 silica gel Inorganic materials 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- XKZQKPRCPNGNFR-UHFFFAOYSA-N 2-(3-hydroxyphenyl)phenol Chemical compound OC1=CC=CC(C=2C(=CC=CC=2)O)=C1 XKZQKPRCPNGNFR-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical group CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 239000002274 desiccant Substances 0.000 description 6
- JBTWLSYIZRCDFO-UHFFFAOYSA-N ethyl methyl carbonate Chemical compound CCOC(=O)OC JBTWLSYIZRCDFO-UHFFFAOYSA-N 0.000 description 6
- 238000000605 extraction Methods 0.000 description 6
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- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 238000005580 one pot reaction Methods 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 4
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 4
- NHFAABIHBNXKDT-UHFFFAOYSA-N 4,5-dihydro-1,3-oxazole;phosphane Chemical compound P.C1CN=CO1 NHFAABIHBNXKDT-UHFFFAOYSA-N 0.000 description 4
- DRSHXJFUUPIBHX-UHFFFAOYSA-N COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 Chemical compound COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 DRSHXJFUUPIBHX-UHFFFAOYSA-N 0.000 description 4
- 239000007810 chemical reaction solvent Substances 0.000 description 4
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- 238000000926 separation method Methods 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical class NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical group CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
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- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- KUXDQQMEFBFTGX-UHFFFAOYSA-N [N].P Chemical compound [N].P KUXDQQMEFBFTGX-UHFFFAOYSA-N 0.000 description 3
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- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- 238000005292 vacuum distillation Methods 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- SICLLPHPVFCNTJ-UHFFFAOYSA-N 1,1,1',1'-tetramethyl-3,3'-spirobi[2h-indene]-5,5'-diol Chemical compound C12=CC(O)=CC=C2C(C)(C)CC11C2=CC(O)=CC=C2C(C)(C)C1 SICLLPHPVFCNTJ-UHFFFAOYSA-N 0.000 description 2
- PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical group CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- NTSLROIKFLNUIJ-UHFFFAOYSA-N 5-Ethyl-2-methylpyridine Chemical compound CCC1=CC=C(C)N=C1 NTSLROIKFLNUIJ-UHFFFAOYSA-N 0.000 description 2
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
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- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 239000005456 alcohol based solvent Substances 0.000 description 2
- 229910000272 alkali metal oxide Inorganic materials 0.000 description 2
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 2
- 150000001342 alkaline earth metals Chemical class 0.000 description 2
- 150000001409 amidines Chemical class 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 150000001448 anilines Chemical class 0.000 description 2
- 125000000732 arylene group Chemical group 0.000 description 2
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
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- XPWWDZRSNFSLRQ-UHFFFAOYSA-N n-dichlorophosphanyl-n-methylmethanamine Chemical compound CN(C)P(Cl)Cl XPWWDZRSNFSLRQ-UHFFFAOYSA-N 0.000 description 2
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- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
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- 125000005428 anthryl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C3C(*)=C([H])C([H])=C([H])C3=C([H])C2=C1[H] 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- ISLOGSAEQNKPGG-UHFFFAOYSA-N beta-Vetivone Chemical compound CC1CC(=O)C=C(C)C11CC(=C(C)C)CC1 ISLOGSAEQNKPGG-UHFFFAOYSA-N 0.000 description 1
- ISLOGSAEQNKPGG-DOMZBBRYSA-N beta-vetivone Natural products C[C@@H]1CC(=O)C=C(C)[C@]11CC(=C(C)C)CC1 ISLOGSAEQNKPGG-DOMZBBRYSA-N 0.000 description 1
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- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
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- XXBDWLFCJWSEKW-UHFFFAOYSA-N dimethylbenzylamine Chemical compound CN(C)CC1=CC=CC=C1 XXBDWLFCJWSEKW-UHFFFAOYSA-N 0.000 description 1
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- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 1
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- AFRJJFRNGGLMDW-UHFFFAOYSA-N lithium amide Chemical compound [Li+].[NH2-] AFRJJFRNGGLMDW-UHFFFAOYSA-N 0.000 description 1
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- XGZVUEUWXADBQD-UHFFFAOYSA-L lithium carbonate Chemical compound [Li+].[Li+].[O-]C([O-])=O XGZVUEUWXADBQD-UHFFFAOYSA-L 0.000 description 1
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- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 238000011017 operating method Methods 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 125000001792 phenanthrenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3C=CC12)* 0.000 description 1
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 description 1
- 150000003053 piperidines Chemical class 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 229960003975 potassium Drugs 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 235000011181 potassium carbonates Nutrition 0.000 description 1
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
- 229910000105 potassium hydride Inorganic materials 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical group [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 229940086066 potassium hydrogencarbonate Drugs 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 150000003212 purines Chemical class 0.000 description 1
- 150000003216 pyrazines Chemical class 0.000 description 1
- 125000001725 pyrenyl group Chemical group 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical group [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 238000012916 structural analysis Methods 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
Images
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- C07C231/12—Preparation of carboxylic acid amides by reactions not involving the formation of carboxamide groups
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Abstract
Description
又は、R1、R4、R5及びR8はそれぞれ独立に水素、C1〜C10アルキル基、C3〜C10シクロアルキル基、C1〜C4アルコキシ基、アリール基、フッ素、塩素、臭素、ヨウ素又はヒドロキシ基であり、R2及びR3はそれらに連結される分子骨格中の炭素原子とともに連結して芳香環を構成し、且つ該芳香環は「R2及びR3に連結される分子骨格中の炭素原子が所在するベンゼン環」とは縮合環構造となり、R6及びR7はそれらに連結される分子骨格中の炭素原子とともに連結して芳香環を構成し、且つ該芳香環は「R6及びR7に連結される分子骨格中の炭素原子が所在するベンゼン環」とは縮合環構造となる。
XはCY1Y2、NY1、O又はSであり、n=0〜3である(ここで、Y1及びY2はそれぞれ独立に水素、C1〜C10アルキル基、C3〜C10シクロアルキル基、アリール基又はC1〜C4アルコキシ基である。)。
且つ、前記式Iで示されるキラル縮合環スピロビインダン骨格化合物は式I−nで示される化合物ではない。)
前記R1’及びR2’はそれぞれ独立にC1〜C10アルキル基又はC3〜C10シクロアルキル基であり、又は前記R1’及びR2’はそれらに連結されるN原子とともに連結してC2〜C10含窒素複素飽和環を構成する。)
下記式の反応経路で示されるように、化合物II−aの製造を例にして、本実施例で、本発明に記載のα,α’−ビス(アリーレン)ケトン化合物(一般式II)の典型的な製造方法を詳細に説明する。
反応基質である式2aで示される化合物における置換基を変更する以外、実施例1と同様な製造方法によって、下記α,α’−ビス(アリーレン)ケトン類化合物II−a〜II−mをそれぞれ製造した。
黄色固体、92%.M.P.142−144℃,1H NMR(400MHz,CDCl3)δ7.91(s,2H),7.26−7.18(m,8H),2.77−2.75(m,4H),2.34(s,6H),1.73−1.67(m,2H),13C NMR(100MHz,CDCl3)δ190.4,137.9,136.7,136.0,135.1,130.1,129.0,128.4,125.3,28.4,23.5,20.0.IR(neat)ν2932,1664,1590,1463,1400,1277,1240,1195,1165,1138,1018,996,968,929,860,814,783,759,736,721,607cm-1.HRMS(ESI)m/z:calcd.for C22H23O+:303.1743,Found:303.1747([M+H]+).
黄色固体、収率85%、M.P.83−85℃,1H NMR(400MHz,CDCl3)δ7.77(s,2H),7.31−7.24(m,6H),7.16−7.14(m,2H),2.94−2.91(m,4H),2.38(s,6H),1.80−1.74(m,2H).13C NMR(100MHz,CDCl3)δ109.3,137.9,137.0,136.0,135.9,131.1,129.4,128.2,127.4,28.5,23.0,21.4.IR(neat)ν2939,1659,1597,1490,1428,1276,1227,1180,1162,1143,1072,1050,971,946,885,835,786,758,737,717,690,616cm-1.HRMS(ESI)m/z:calcd.for C22H23O+:303.1743,Found:303.1751([M+H]+).
黄色固体、収率90%.M.P.179−181℃,1H NMR(400MHz,CDCl3)δ7.78(s,2H),7.38(d,J=8.0Hz,4H),7.21(d,J=8.4Hz,4H),2.92(t,J=6Hz,4H),2.38(s,6H),1.81−1.75(m,2H).13C NMR(100MHz,CDCl3)δ190.4,138.8,136.8,135.4,133.1,130.4,129.1,28.5,23.0,21.4.IR(neat)ν2938,2915,1660,1598,1564,1507,1311,1266,1197,1154,1139,1016,958,935,867,817,757,729,706,660cm-1.HRMS(ESI)m/z:calcd.for C22H23O+:303.1743,Found:303.1749([M+H]+).
黄色固体、収率95%、1H NMR(400MHz,CDCl3)δ7.76(s,2H),7.32(t,J=8.0Hz,2H),7.06(d,J=7.6Hz,2H),6.99(s,2H),6.89(dd,J=8,2.4Hz,2H),3.83(s,6H),2.94−2.91(m,4H),1.81−1.75(m,2H).13C NMR(100MHz,CDCl3)δ190.3,159.4,137.2,136.8,136.4,129.3,122.8,115.7,114.2,55.2,28.4,22.9,IR(neat)ν2934,2834,1690,1601,1571,1491,1445,1426,1316,1270,1220,1185,1162,1094,1045,993,947,921,883,868,822,769,751,674,626cm-1.HRMS(ESI)m/z:calcd.for C22H23O3 +:335.1642,Found:335.1646([M+H]+).
黄色固体、収率90%、M.P.167−169℃、1H NMR(400MHz,CDCl3)δ7.76(s,2H),7.44(d,J=8.8Hz,4H),6.92(d,J=8.8Hz,4H),3.82(s,6H),2.89(t,J=5.2Hz,4H),1.83−1.75(m,2H).13C NMR(100MHz,CDCl3)δ190.0,159.8,136.4,134.2,132.1,128.6,113.8,55.2,28.4,22.9.IR(neat)ν2939,2829,1657,1591,1553,1505,1451,1416,1313,1301,1276,1247,1182,1159,1138,1112,1022,965,948,868,832,809,754,731,663cm-1.HRMS(ESI)m/z:calcd.for C22H23O3 +:335.1642,Found:335.1647([M+H]+).
アルゴンガス雰囲気下、水素化フラスコ(150−mL)を無水・無酸素条件下で処理した後、実施例2で製造された化合物II−h(0.1g、0.2mmol)、触媒A(0.002mmol)、及び無水ジクロロメタン(5mL)を投入した。グローブボックスにおいて水素化フラスコをオートクレーブに移して、水素ガスを3回置換した後、水素ガスを導入して、室温で12時間反応させた。ヒュームフードにおいて残留水素ガスを慎重に排出して、反応釜を開き、溶媒を減圧除去して、混合物をサンプリングして1H NMRにより、II−hの転化率と生成物III−hのシス−トランス比率(d.r.=anti/syn)を測定した。余剰混合物から溶媒を減圧除去して、残留物をシリカゲルカラムクロマトグラフィーにより分離精製して(石油エーテル/酢酸エチル20:1)、無色油状液体III−hを得て、生成物のee値とdr値はいずれも実施例3におけるキラル高速液体クロマトグラフィー方法によって測定された。触媒の種類と水素ガス圧力、生成物収率、dr値及びee値は表1に示される。
アルゴンガス雰囲気下、50−mLシュレンク管(Schlenk管)に化合物III−h(ee、>99%、247mg、0.5mmol)と無水ジクロロメタン(10mL)を投入して、溶液を氷浴中0℃に冷却させて、緩慢に触媒(本実施例では、触媒はTiCl4である)(0.11mL、1.0mmol)を加えて、0℃で30分間撹拌後、緩慢に室温に昇温して、5時間撹拌し続け、TLCにより検反応終了と検出されると、5mLの水を加えて反応をクエンチさせた。反応混合物をジクロロメタン(5mL×3)で3回抽出して、有機相を合併し、無水硫酸ナトリウムで乾燥させて、乾燥剤を濾過除去し、濾液から溶媒を減圧除去した後、残留物をシリカゲルカラムクロマトグラフィーにより分離精製して(石油エーテル/酢酸エチル=50:1)、白色固体(1S,2S,2’S)−I−hを得て、生成物のee値を、キラルHPLCにより測定した[Chiralcel OD−H column;移動相、イソプロパノール/ノルマルヘキサン=0:100、温度、室温.;移動相流速、0.8mL/min;紫外線−可視光検出波長λ=230nm;tR(major)=15.80min;tR(minor)=23.00min.]。
表3に示されるように、基質化合物III−hの使用量(本実施例では0.2mmol)、触媒の種類と使用量、溶媒の種類と使用量(本実施例では、溶媒の使用量はいずれも2.0mLである)、反応温度を変更する以外、実施例6と同様な方法によって実験を行い、収率とee値を表3に示す。表3中、モル当量は、化合物III−hのモル量に対する触媒のモル量の倍数である。表3中、ee値の欄において、「−」は測定不可を意味する。
表4に示されるように、基質化合物III−hの使用量(本実施例では0.2mmol)、触媒の種類と使用量、溶媒の種類と使用量(本実施例では、溶媒の使用量はいずれも2.0mLである)、反応温度を変更する以外、実施例6と同様な方法によって実験を行い、収率とee値を表4に示す。表4中、モル当量は、触媒のモル量の化合物III−hのモル量に対する倍数である。
化合物IIを原料として、不斉水素化と環化ワンポット法によって、中間体化合物IIIを分離せずに、水素化反応混合物に適量のTiCl4を加えて、化合物Iを合成した。本実施例では、化合物II−hのワンポット法による不斉水素化−環化反応を用いた化合物I−hの合成を例にして、化合物IIを出発材料としてワンポット法により化合物Iを合成する実験の典型的な操作方法を説明した。
実施例28と29の前記実験方法を参照して操作し、(R)−tBuPHOX/Ir(I)を不斉水素化触媒として、キラル縮合環スピロビインダン骨格ジフェノールI−pを得た。
実施例28と29の前記実験方法を参照して操作し、(R)−tBuPHOX/Ir(I)を不斉水素化触媒として、キラル縮合環スピロビインダン骨格ジフェノールI−qを得た。
実施例28と29の前記実験方法を参照して操作し、(R)−tBuPHOX/Ir(I)を不斉水素化触媒として、キラル縮合環スピロビインダン骨格ジフェノールI−rを得た。
実施例28と29の前記実験方法を参照して操作し、(R)−tBuPHOX/Ir(I)を不斉水素化触媒として、キラル縮合環スピロビインダン骨格ジフェノールI−sを得た。
Claims (18)
- 式Iで示されるキラル縮合環スピロビインダン骨格化合物、またはそのエナンチオマー若しくはジアステレオマー。
又は、R1、R4、R5及びR8はそれぞれ独立に水素、C1〜C10アルキル基、C3〜C10シクロアルキル基、C1〜C4アルコキシ基、アリール基、フッ素、塩素、臭素、ヨウ素又はヒドロキシ基であり、R2及びR3はそれらに連結される分子骨格中の炭素原子とともに連結して芳香環を構成し、且つ該芳香環は「R2及びR3に連結される分子骨格中の炭素原子が所在するベンゼン環」とは縮合環構造となり、R6及びR7はそれらに連結される分子骨格中の炭素原子とともに連結して芳香環を構成し、且つ該芳香環は「R6及びR7に連結される分子骨格中の炭素原子が所在するベンゼン環」とは縮合環構造となる。
XはCY1Y2、NY1、O又はSであり、n=0〜3である(ここで、Y1及びY2はそれぞれ独立に水素、C1〜C10アルキル基、C3〜C10シクロアルキル基、アリール基又はC1〜C4アルコキシ基である。)。
且つ、前記式Iで示されるキラル縮合環スピロビインダン骨格化合物は式I−nで示される化合物ではない。)
- 前記R1とR8は同じであり、及び/又は、前記R2とR7は同じであり、及び/又は、前記R3とR6は同じであり、及び/又は、前記R4とR5は同じであり、及び/又は、前記n=0、1、2又は3であることを特徴とする請求項1に記載の化合物。
- 前記R1、R2、R3、R4、R5、R6、R7及びR8がそれぞれ独立にC1〜C10アルキル基である場合、前記C1〜C10アルキル基はC1〜C6アルキル基であり、
前記R1、R2、R3、R4、R5、R6、R7及びR8がそれぞれ独立にC3〜C10シクロアルキル基である場合、前記C3〜C10シクロアルキル基はC3〜C6シクロアルキル基であり、
前記R1、R2、R3、R4、R5、R6、R7及びR8がそれぞれ独立にC1〜C4アルコキシ基である場合、前記C1〜C4アルコキシ基はC1〜C3アルコキシ基であり、
前記R1、R2、R3、R4、R5、R6、R7及びR8がそれぞれ独立にアリール基である場合、前記アリール基はC6〜C20アリール基であり、
前記R2及びR3が、それらに連結される分子骨格中の炭素原子とともに連結して芳香環を構成する場合、前記芳香環はC6〜C20芳香環であり、
前記R6及びR7が、それらに連結される分子骨格中の炭素原子とともに連結して芳香環を構成する場合、前記芳香環はC6〜C20芳香環であり、
前記Y1及びY2がそれぞれ独立にC1〜C10アルキル基である場合、前記C1〜C10アルキル基はC1〜C4アルキル基であり、
前記Y1及びY2がそれぞれ独立にC3〜C10シクロアルキル基である場合、前記C3〜C10シクロアルキル基はC3〜C6シクロアルキル基であり、
前記Y1及びY2がそれぞれ独立にアリール基である場合、前記アリール基はC6〜C20アリール基であり、
前記Y1及びY2がそれぞれ独立にC1〜C4アルコキシ基である場合、前記C1〜C4アルコキシ基はメトキシ基又はエトキシ基であることを特徴とする請求項1又は2に記載の化合物。 - 前記R1、R2、R3、R4、R6、R6、R7及びR8がそれぞれ独立にC1〜C6アルキル基である場合、前記C1〜C6アルキル基はC1〜C3アルキル基であり、
前記R1、R2、R3、R4、R5、R6、R7及びR8がそれぞれ独立にC3〜C6シクロアルキル基である場合、前記C3〜C6シクロアルキル基はシクロプロピル基であり、
前記R1、R2、R3、R4、R5、R6、R7及びR8がそれぞれ独立にC1〜C3アルコキシ基である場合、前記C1〜C3アルコキシ基はメトキシ基、エトキシ基又はプロポキシ基であり、
前記R1、R2、R3、R4、R5、R6、R7及びR8がそれぞれ独立に前記C6〜C20アリール基である場合、前記C6〜C20アリール基はC6〜C12アリール基であり、
前記R2及びR3が、それらに連結される分子骨格中の炭素原子とともに連結して前記C6〜C20芳香環を構成する場合、前記C6〜C20芳香環はC6〜C12芳香環であり、
前記R6及びR7が、それらに連結される分子骨格中の炭素原子とともに連結してC6〜C20芳香環を構成する場合、前記C6〜C20芳香環はC6〜C12芳香環であり、
前記Y1及びY2がそれぞれ独立にC1〜C4アルキル基である場合、前記C1〜C4アルキル基はメチル基、エチル基、プロピル基又はtert−ブチル基であり、
前記Y1及びY2がそれぞれ独立にC3〜C6シクロアルキル基である場合、前記C3〜C6シクロアルキル基はシクロプロピル基であり、
前記Y1及びY2がそれぞれ独立にC6〜C20アリール基である場合、前記C6〜C20アリール基はC6〜C12アリール基であることを特徴とする請求項3に記載の化合物。 - 前記R1、R2、R3、R4、R5、R6、R7及びR8がそれぞれ独立にC1〜C3アルキル基である場合、前記C1〜C3アルキル基はメチル基、エチル基又はプロピル基であり、
前記R1、R2、R3、R4、R5、R6、R7及びR8がそれぞれ独立に前記C6〜C12アリール基である場合、前記C6〜C12はフェニル基又はナフチル基であり、
前記R2及びR3が、それらに連結される分子骨格中の炭素原子とともに連結して前記C6〜C12芳香環を構成する場合、前記C6〜C12芳香環はベンゼン環又はナフタレン環であり、
前記R6及びR7が、それらに連結される分子骨格中の炭素原子とともに連結してC6〜C12芳香環を構成する場合、前記C6〜C12芳香環はベンゼン環又はナフタレン環であり、
前記Y1及びY2がそれぞれ独立にC6〜C12アリール基である場合、前記C6〜C12アリール基はフェニル基又はナフチル基であることを特徴とする請求項4に記載の化合物。 - 前記R1’及びR2’がそれぞれ独立にC1〜C10アルキル基である場合、前記C1〜C10アルキル基はC1〜C3アルキル基であり、
前記R1’及びR2’がそれぞれ独立にC3〜C10シクロアルキル基である場合、前記C3〜C10シクロアルキル基はC3〜C6シクロアルキル基であり、
前記R1’及びR2’が、それらに連結されるN原子とともに連結してC2〜C10含窒素複素飽和環を構成する場合、前記C2〜C10含窒素複素飽和環はC3〜C6含窒素複素飽和環であることを特徴とする請求項7に記載の式I’で示されるホスホロアミダイトリガンド、またはそのエナンチオマー若しくはジアステレオマー。 - 前記R1’及びR2’がそれぞれ独立にC1〜C3アルキル基である場合、前記C1〜C3アルキル基はメチル基、エチル基又はプロピル基であり、
前記R1’及びR2’がそれぞれ独立にC3〜C6シクロアルキル基である場合、前記C3〜C6シクロアルキル基はシクロプロピル基であり、
前記R1’及びR2’が、それらに連結されるN原子とともに連結してC3〜C6含窒素複素飽和環を構成する場合、前記C3〜C6含窒素複素飽和環はピラゾリジンであることを特徴とする請求項8に記載の式I’で示されるホスホロアミダイトリガンド、またはそのエナンチオマー若しくはジアステレオマー。 - 前記ブレンステッド酸は、塩酸、リン酸、ポリリン酸、メタンスルホン酸、トリフルオロメタンスルホン酸、酢酸、トリフルオロ酢酸、p−トルエンスルホン酸及びリンタングステン酸のうちの1種又は複数種であり、前記ルイス酸はトリフルオロメタンスルホン酸スカンジウム、三塩化アルミニウム、四塩化錫、三塩化鉄、三フッ化ホウ素、四塩化チタン、テトライソプロピルチタネート、トリフルオロメタンスルホン酸インジウム及びトリフルオロメタンスルホン酸銅のうちの1種又は複数種であり、
及び/又は、前記式Iで示される化合物の製造方法はさらに、前記溶媒と前記式IIIで示される化合物を混合して、0℃条件において、前記触媒を添加して1〜100分間反応させ、15℃〜40℃に自然昇温して1〜20時間引き続き反応させるステップを含み、
及び/又は、前記分子内フリーデル・クラフツ反応は、無水・無酸素条件において行われ、
及び/又は、前記分子内フリーデル・クラフツ反応は、保護性ガスの存在下において行われ、
及び/又は、前記式IIIで示される化合物と前記触媒のモル比は100:1〜1:100であり、
及び/又は、前記分子内フリーデル・クラフツ反応の溶媒は、芳香族炭化水素系溶媒、ハロゲン化炭化水素系溶媒、エーテル系溶媒、アルコール系溶媒、アミド系溶媒及びスルホキシド系溶媒のうちの1種又は複数種であり、
及び/又は、前記式IIIで示される化合物と前記分子内フリーデル・クラフツ反応の溶媒とのモル体積比は0.02mol/L〜0.2mol/Lであり、
及び/又は、前記分子内フリーデル・クラフツ反応の温度は−40℃〜100℃であり、
及び/又は、前記分子内フリーデル・クラフツ反応の時間は0.1〜48時間であることを特徴とする請求項11に記載の製造方法。 - 前記式Iで示される化合物の製造方法において、前記不斉水素化反応の触媒は、ルテニウム、ロジウム、イリジウム及びパラジウムの遷移金属錯体のうちの1種又は複数種であり、前記金属錯体はキラル又はアキラルであり、
及び/又は、前記式Iで示される化合物の製造方法において、前記不斉水素化反応の触媒と前記式IIで示される化合物とのモル比は0.0001〜0.1であり、
及び/又は、前記式Iで示される化合物の製造方法において、前記不斉水素化反応の溶媒はハロゲン化炭化水素系溶媒、芳香炭化水素系溶媒、エーテル系溶媒、アルコール系溶媒、アミド系溶媒及びスルホキシド系溶媒のうちの1種又は複数種であり、
及び/又は、前記式Iで示される化合物の製造方法において、前記不斉水素化反応の溶媒と前記式IIで示される化合物との体積質量比は1ml/g〜20ml/gであり、
及び/又は、前記式Iで示される化合物の製造方法において、前記不斉水素化反応の水素ガスの圧力は1〜100atmであり、
及び/又は、前記式Iで示される化合物の製造方法において、前記不斉水素化反応の温度は−78〜80℃であり、
及び/又は、前記式Iで示される化合物の製造方法において、前記不斉水素化反応の時間は1〜48時間であり、
及び/又は、前記式Iで示される化合物の製造方法において、前記不斉水素化反応終了後、後処理を行わずに、反応系をそのまま、前記フリーデル・クラフツ反応の溶媒、触媒及び前記式IIIで示される化合物と混合して、前記分子内フリーデル・クラフツ反応を行うことを特徴とする請求項13に記載の製造方法。 - 前記アルドール縮合反応は、アルカリ性条件において行われ、
及び/又は、前記アルドール縮合反応の溶媒はアルコール系溶媒と水の混合溶媒であり、
及び/又は、前記アルドール縮合反応の溶媒と前記式VIで示される化合物との体積モル比は10000ml/mol〜1ml/molであり、
及び/又は、前記アルドール縮合反応の温度は10〜35℃であり、
及び/又は、前記置換反応の時間は1〜12時間であることを特徴とする請求項15に記載の製造方法。 - 前記式I’で示される化合物の製造方法はさらに、アルカリ性条件において、前記式Iで示される化合物を前記溶媒と混合して、−40〜10℃に冷却させ、次に前記式IVで示される化合物と混合し、温度を10〜35℃に上げてから、前記置換反応を行うステップを含み、
及び/又は、前記置換反応は、無水・無酸素条件において行われ、
及び/又は、前記置換反応は、保護性ガスの存在下において行われ、
及び/又は、前記アルカリ性条件は、反応をアルカリの作用下で行うことであり、
及び/又は、前記置換反応の溶媒は、エーテル系溶媒、ハロ置換アルカン系溶媒及び芳香族炭化水素系溶媒のうちの1種又は複数種であり、
及び/又は、前記置換反応において、前記式Iで示される化合物と前記溶媒とのモル体積比は0.05mol/L〜0.5mol/Lであり、
及び/又は、前記置換反応において、前記式Iで示される化合物と式IVで示される化合物とのモル比は1:1.1〜1:3であり、
及び/又は、前記置換反応の温度は0〜35℃であり、
及び/又は、前記置換反応の時間は1〜12時間であることを特徴とする請求項17に記載の製造方法。
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Non-Patent Citations (8)
Title |
---|
ACTA CRYST., vol. E64, JPN6019015259, 2008, pages 455, ISSN: 0004315268 * |
ADV. SYNTH. CATAL, vol. 352, JPN6019015258, 2010, pages 103 - 107, ISSN: 0004315267 * |
CHEM. COMMUN., JPN6019015275, 2002, pages 480 - 481, ISSN: 0004315271 * |
E-EROS ENCYCLOPEDIA OF REAGENTS FOR ORGANIC SYNTHESIS, JPN6019015272, 2010, pages 1 - 4, ISSN: 0004315270 * |
J AM CHEM SOC, vol. 133(14), JPN6019015271, 2011, pages 5500 - 5507, ISSN: 0004315269 * |
J. ORG. CHEM., vol. 69, JPN6019015280, 2004, pages 4648 - 4655, ISSN: 0004315273 * |
TETRAHEDORON:ASYMMETRY, vol. 15, JPN6019015255, 2004, pages 3427 - 3431, ISSN: 0004315266 * |
TETRAHEDRON:ASYMMETRY, vol. 14, JPN6019015278, 2003, pages 3219 - 3224, ISSN: 0004315272 * |
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