JP5689111B2 - 触媒的ウィッティヒ及び光延反応 - Google Patents
触媒的ウィッティヒ及び光延反応 Download PDFInfo
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- JP5689111B2 JP5689111B2 JP2012504783A JP2012504783A JP5689111B2 JP 5689111 B2 JP5689111 B2 JP 5689111B2 JP 2012504783 A JP2012504783 A JP 2012504783A JP 2012504783 A JP2012504783 A JP 2012504783A JP 5689111 B2 JP5689111 B2 JP 5689111B2
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- Prior art keywords
- mmol
- phosphine
- reaction
- catalytic
- phosphine oxide
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 230000003197 catalytic effect Effects 0.000 title claims description 55
- 238000007239 Wittig reaction Methods 0.000 title description 25
- 238000006751 Mitsunobu reaction Methods 0.000 title description 13
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims description 84
- AUONHKJOIZSQGR-UHFFFAOYSA-N oxophosphane Chemical compound P=O AUONHKJOIZSQGR-UHFFFAOYSA-N 0.000 claims description 50
- 238000000034 method Methods 0.000 claims description 48
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims description 42
- VDCSGNNYCFPWFK-UHFFFAOYSA-N diphenylsilane Chemical compound C=1C=CC=CC=1[SiH2]C1=CC=CC=C1 VDCSGNNYCFPWFK-UHFFFAOYSA-N 0.000 claims description 32
- XYFCBTPGUUZFHI-UHFFFAOYSA-O phosphonium Chemical compound [PH4+] XYFCBTPGUUZFHI-UHFFFAOYSA-O 0.000 claims description 18
- 230000008569 process Effects 0.000 claims description 18
- 150000001299 aldehydes Chemical class 0.000 claims description 16
- KGPGYLRWXHHPJH-UHFFFAOYSA-N CC1=CC=CC([PH2]=O)=C1 Chemical group CC1=CC=CC([PH2]=O)=C1 KGPGYLRWXHHPJH-UHFFFAOYSA-N 0.000 claims description 15
- 150000001336 alkenes Chemical class 0.000 claims description 14
- 239000003638 chemical reducing agent Substances 0.000 claims description 13
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 claims description 11
- 229910000077 silane Inorganic materials 0.000 claims description 11
- MPQXHAGKBWFSNV-UHFFFAOYSA-N oxidophosphanium Chemical class [PH3]=O MPQXHAGKBWFSNV-UHFFFAOYSA-N 0.000 claims description 10
- PARWUHTVGZSQPD-UHFFFAOYSA-N phenylsilane Chemical compound [SiH3]C1=CC=CC=C1 PARWUHTVGZSQPD-UHFFFAOYSA-N 0.000 claims description 10
- 150000002576 ketones Chemical class 0.000 claims description 9
- 150000002148 esters Chemical class 0.000 claims description 8
- 239000002243 precursor Substances 0.000 claims description 7
- 150000004714 phosphonium salts Chemical group 0.000 claims description 5
- 230000005595 deprotonation Effects 0.000 claims description 4
- 238000010537 deprotonation reaction Methods 0.000 claims description 4
- 150000008282 halocarbons Chemical class 0.000 claims description 4
- YUYCVXFAYWRXLS-UHFFFAOYSA-N trimethoxysilane Chemical compound CO[SiH](OC)OC YUYCVXFAYWRXLS-UHFFFAOYSA-N 0.000 claims description 4
- AKQNYQDSIDKVJZ-UHFFFAOYSA-N triphenylsilane Chemical compound C1=CC=CC=C1[SiH](C=1C=CC=CC=1)C1=CC=CC=C1 AKQNYQDSIDKVJZ-UHFFFAOYSA-N 0.000 claims description 4
- 125000004122 cyclic group Chemical group 0.000 claims description 3
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 claims 2
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 87
- 238000006243 chemical reaction Methods 0.000 description 52
- UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Substances C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 46
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 42
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 36
- 230000009467 reduction Effects 0.000 description 26
- 238000006722 reduction reaction Methods 0.000 description 26
- 230000015572 biosynthetic process Effects 0.000 description 22
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
- 229910000029 sodium carbonate Inorganic materials 0.000 description 21
- 238000003818 flash chromatography Methods 0.000 description 20
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 18
- 239000012043 crude product Substances 0.000 description 18
- 239000000047 product Substances 0.000 description 18
- 239000002904 solvent Substances 0.000 description 14
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 12
- 239000006227 byproduct Substances 0.000 description 12
- 150000001875 compounds Chemical class 0.000 description 12
- 239000012230 colorless oil Substances 0.000 description 11
- YDCHPLOFQATIDS-UHFFFAOYSA-N methyl 2-bromoacetate Chemical compound COC(=O)CBr YDCHPLOFQATIDS-UHFFFAOYSA-N 0.000 description 11
- 239000007787 solid Substances 0.000 description 10
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 9
- 150000003003 phosphines Chemical class 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- 239000000203 mixture Substances 0.000 description 8
- 229910052698 phosphorus Inorganic materials 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 8
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 7
- 150000001412 amines Chemical class 0.000 description 7
- 238000011161 development Methods 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 238000006772 olefination reaction Methods 0.000 description 7
- 239000011574 phosphorus Substances 0.000 description 7
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 229910052786 argon Inorganic materials 0.000 description 6
- NEHNMFOYXAPHSD-UHFFFAOYSA-N citronellal Chemical compound O=CCC(C)CCC=C(C)C NEHNMFOYXAPHSD-UHFFFAOYSA-N 0.000 description 6
- 238000011156 evaluation Methods 0.000 description 6
- 230000007246 mechanism Effects 0.000 description 6
- 229910052723 transition metal Inorganic materials 0.000 description 6
- 150000003624 transition metals Chemical class 0.000 description 6
- ZDHXKXAHOVTTAH-UHFFFAOYSA-N trichlorosilane Chemical compound Cl[SiH](Cl)Cl ZDHXKXAHOVTTAH-UHFFFAOYSA-N 0.000 description 6
- 239000005052 trichlorosilane Substances 0.000 description 6
- REXUYBKPWIPONM-UHFFFAOYSA-N 2-bromoacetonitrile Chemical compound BrCC#N REXUYBKPWIPONM-UHFFFAOYSA-N 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- -1 azo compound Chemical class 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 5
- CCRCUPLGCSFEDV-BQYQJAHWSA-N methyl trans-cinnamate Chemical compound COC(=O)\C=C\C1=CC=CC=C1 CCRCUPLGCSFEDV-BQYQJAHWSA-N 0.000 description 5
- 239000012041 precatalyst Substances 0.000 description 5
- RSJKGSCJYJTIGS-UHFFFAOYSA-N undecane Chemical compound CCCCCCCCCCC RSJKGSCJYJTIGS-UHFFFAOYSA-N 0.000 description 5
- YMKWWHFRGALXLE-UHFFFAOYSA-N 4-methyl-1-phenyl-2,3-dihydro-1$l^{5}-phosphole 1-oxide Chemical compound C1CC(C)=CP1(=O)C1=CC=CC=C1 YMKWWHFRGALXLE-UHFFFAOYSA-N 0.000 description 4
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 4
- PJANXHGTPQOBST-VAWYXSNFSA-N Stilbene Natural products C=1C=CC=CC=1/C=C/C1=CC=CC=C1 PJANXHGTPQOBST-VAWYXSNFSA-N 0.000 description 4
- 229910052785 arsenic Inorganic materials 0.000 description 4
- RQNWIZPPADIBDY-UHFFFAOYSA-N arsenic atom Chemical compound [As] RQNWIZPPADIBDY-UHFFFAOYSA-N 0.000 description 4
- 239000012298 atmosphere Substances 0.000 description 4
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 4
- 238000013461 design Methods 0.000 description 4
- 238000006317 isomerization reaction Methods 0.000 description 4
- 238000011068 loading method Methods 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- MDDUHVRJJAFRAU-YZNNVMRBSA-N tert-butyl-[(1r,3s,5z)-3-[tert-butyl(dimethyl)silyl]oxy-5-(2-diphenylphosphorylethylidene)-4-methylidenecyclohexyl]oxy-dimethylsilane Chemical compound C1[C@@H](O[Si](C)(C)C(C)(C)C)C[C@H](O[Si](C)(C)C(C)(C)C)C(=C)\C1=C/CP(=O)(C=1C=CC=CC=1)C1=CC=CC=C1 MDDUHVRJJAFRAU-YZNNVMRBSA-N 0.000 description 4
- ZWKNLRXFUTWSOY-QPJJXVBHSA-N (e)-3-phenylprop-2-enenitrile Chemical compound N#C\C=C\C1=CC=CC=C1 ZWKNLRXFUTWSOY-QPJJXVBHSA-N 0.000 description 3
- VEBCSALPNMISTC-UHFFFAOYSA-N 3-cyclohexylprop-2-enenitrile Chemical compound N#CC=CC1CCCCC1 VEBCSALPNMISTC-UHFFFAOYSA-N 0.000 description 3
- CONLQGNBFRQUBX-UHFFFAOYSA-N 3-thiophen-2-ylprop-2-enenitrile Chemical compound N#CC=CC1=CC=CS1 CONLQGNBFRQUBX-UHFFFAOYSA-N 0.000 description 3
- PBXPWAOTBQNSHR-UHFFFAOYSA-N 5,9-dimethyldeca-2,8-dienenitrile Chemical compound CC(C)=CCCC(C)CC=CC#N PBXPWAOTBQNSHR-UHFFFAOYSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- 238000006555 catalytic reaction Methods 0.000 description 3
- 229930003633 citronellal Natural products 0.000 description 3
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- 238000005516 engineering process Methods 0.000 description 3
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- QILOUBBQVGUFNG-CMDGGOBGSA-N methyl (e)-2-methyl-3-phenylprop-2-enoate Chemical compound COC(=O)C(\C)=C\C1=CC=CC=C1 QILOUBBQVGUFNG-CMDGGOBGSA-N 0.000 description 3
- FVSMIMXZNUZTOE-BQYQJAHWSA-N methyl (e)-3-(2-methylphenyl)prop-2-enoate Chemical compound COC(=O)\C=C\C1=CC=CC=C1C FVSMIMXZNUZTOE-BQYQJAHWSA-N 0.000 description 3
- NVXKMHUNXMXXDM-QPJJXVBHSA-N methyl (e)-3-(4-nitrophenyl)prop-2-enoate Chemical compound COC(=O)\C=C\C1=CC=C([N+]([O-])=O)C=C1 NVXKMHUNXMXXDM-QPJJXVBHSA-N 0.000 description 3
- 150000002894 organic compounds Chemical class 0.000 description 3
- JONKIUBSNSUGGZ-UHFFFAOYSA-N oxaphosphetane Chemical compound C1CPO1 JONKIUBSNSUGGZ-UHFFFAOYSA-N 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
- 230000037361 pathway Effects 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 150000004756 silanes Chemical class 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- PJANXHGTPQOBST-UHFFFAOYSA-N stilbene Chemical compound C=1C=CC=CC=1C=CC1=CC=CC=C1 PJANXHGTPQOBST-UHFFFAOYSA-N 0.000 description 3
- 235000021286 stilbenes Nutrition 0.000 description 3
- 229910052714 tellurium Inorganic materials 0.000 description 3
- PORWMNRCUJJQNO-UHFFFAOYSA-N tellurium atom Chemical compound [Te] PORWMNRCUJJQNO-UHFFFAOYSA-N 0.000 description 3
- 239000002699 waste material Substances 0.000 description 3
- 238000007106 1,2-cycloaddition reaction Methods 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 2
- IQQDLHGWGKEQDS-VOTSOKGWSA-N Methyl 2-heptenoate Chemical compound CCCC\C=C\C(=O)OC IQQDLHGWGKEQDS-VOTSOKGWSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 229910052787 antimony Inorganic materials 0.000 description 2
- WATWJIUSRGPENY-UHFFFAOYSA-N antimony atom Chemical compound [Sb] WATWJIUSRGPENY-UHFFFAOYSA-N 0.000 description 2
- 150000001540 azides Chemical class 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- CCRCUPLGCSFEDV-UHFFFAOYSA-N cinnamic acid methyl ester Natural products COC(=O)C=CC1=CC=CC=C1 CCRCUPLGCSFEDV-UHFFFAOYSA-N 0.000 description 2
- PJANXHGTPQOBST-QXMHVHEDSA-N cis-stilbene Chemical compound C=1C=CC=CC=1/C=C\C1=CC=CC=C1 PJANXHGTPQOBST-QXMHVHEDSA-N 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- KVFDZFBHBWTVID-UHFFFAOYSA-N cyclohexanecarbaldehyde Chemical compound O=CC1CCCCC1 KVFDZFBHBWTVID-UHFFFAOYSA-N 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- CNUDBTRUORMMPA-UHFFFAOYSA-N formylthiophene Chemical compound O=CC1=CC=CS1 CNUDBTRUORMMPA-UHFFFAOYSA-N 0.000 description 2
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 2
- KWIUHFFTVRNATP-UHFFFAOYSA-N glycine betaine Chemical compound C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 2
- 150000004820 halides Chemical class 0.000 description 2
- 238000005984 hydrogenation reaction Methods 0.000 description 2
- 239000012280 lithium aluminium hydride Substances 0.000 description 2
- 238000005649 metathesis reaction Methods 0.000 description 2
- JGUOUUUTXGGCGA-UXBLZVDNSA-N methyl (2e)-5,9-dimethyldeca-2,8-dienoate Chemical compound COC(=O)\C=C\CC(C)CCC=C(C)C JGUOUUUTXGGCGA-UXBLZVDNSA-N 0.000 description 2
- OXWQBUHCJNXFLV-NXZHAISVSA-N methyl (2e,4e)-5-phenylpenta-2,4-dienoate Chemical compound COC(=O)\C=C\C=C\C1=CC=CC=C1 OXWQBUHCJNXFLV-NXZHAISVSA-N 0.000 description 2
- YUEFITCWDISQAO-QPJJXVBHSA-N methyl (e)-3-[4-(trifluoromethyl)phenyl]prop-2-enoate Chemical compound COC(=O)\C=C\C1=CC=C(C(F)(F)F)C=C1 YUEFITCWDISQAO-QPJJXVBHSA-N 0.000 description 2
- QABLOFMHHSOFRJ-UHFFFAOYSA-N methyl 2-chloroacetate Chemical compound COC(=O)CCl QABLOFMHHSOFRJ-UHFFFAOYSA-N 0.000 description 2
- ZNJMTZNUYPTNLN-UHFFFAOYSA-N methyl 3-(2,6-dichlorophenyl)prop-2-enoate Chemical compound COC(=O)C=CC1=C(Cl)C=CC=C1Cl ZNJMTZNUYPTNLN-UHFFFAOYSA-N 0.000 description 2
- VWHFZNARASKJAS-UHFFFAOYSA-N methyl 4-(2-phenylethenyl)benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C=CC1=CC=CC=C1 VWHFZNARASKJAS-UHFFFAOYSA-N 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 229930014626 natural product Natural products 0.000 description 2
- BTFQKIATRPGRBS-UHFFFAOYSA-N o-tolualdehyde Chemical compound CC1=CC=CC=C1C=O BTFQKIATRPGRBS-UHFFFAOYSA-N 0.000 description 2
- 238000006362 organocatalysis Methods 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- 239000004810 polytetrafluoroethylene Substances 0.000 description 2
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- ZYEMNJWJLARYJR-UHFFFAOYSA-M sodium;tert-butyl carbonate Chemical group [Na+].CC(C)(C)OC([O-])=O ZYEMNJWJLARYJR-UHFFFAOYSA-M 0.000 description 2
- 239000002594 sorbent Substances 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
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- 231100000331 toxic Toxicity 0.000 description 2
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- DQFBYFPFKXHELB-VAWYXSNFSA-N trans-chalcone Chemical compound C=1C=CC=CC=1C(=O)\C=C\C1=CC=CC=C1 DQFBYFPFKXHELB-VAWYXSNFSA-N 0.000 description 2
- FIQMHBFVRAXMOP-UHFFFAOYSA-N triphenylphosphane oxide Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=O)C1=CC=CC=C1 FIQMHBFVRAXMOP-UHFFFAOYSA-N 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- KJPRLNWUNMBNBZ-QPJJXVBHSA-N (E)-cinnamaldehyde Chemical compound O=C\C=C\C1=CC=CC=C1 KJPRLNWUNMBNBZ-QPJJXVBHSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- PTMWTBRUBHYQBO-UHFFFAOYSA-N 1-(2-phenylethenyl)-4-(trifluoromethyl)benzene Chemical group C1=CC(C(F)(F)F)=CC=C1C=CC1=CC=CC=C1 PTMWTBRUBHYQBO-UHFFFAOYSA-N 0.000 description 1
- DMIYKWPEFRFTPY-UHFFFAOYSA-N 2,6-dichlorobenzaldehyde Chemical compound ClC1=CC=CC(Cl)=C1C=O DMIYKWPEFRFTPY-UHFFFAOYSA-N 0.000 description 1
- 239000001431 2-methylbenzaldehyde Substances 0.000 description 1
- NMWVKRPDPIADRN-UHFFFAOYSA-N 3-methyl-1-phenyl-1$l^{5}-phospholane 1-oxide Chemical compound C1C(C)CCP1(=O)C1=CC=CC=C1 NMWVKRPDPIADRN-UHFFFAOYSA-N 0.000 description 1
- CSDQQAQKBAQLLE-UHFFFAOYSA-N 4-(4-chlorophenyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine Chemical compound C1=CC(Cl)=CC=C1C1C(C=CS2)=C2CCN1 CSDQQAQKBAQLLE-UHFFFAOYSA-N 0.000 description 1
- BEOBZEOPTQQELP-UHFFFAOYSA-N 4-(trifluoromethyl)benzaldehyde Chemical compound FC(F)(F)C1=CC=C(C=O)C=C1 BEOBZEOPTQQELP-UHFFFAOYSA-N 0.000 description 1
- PDONIKHDXYHTLS-UHFFFAOYSA-N 4-bromothiophene-2-carbaldehyde Chemical compound BrC1=CSC(C=O)=C1 PDONIKHDXYHTLS-UHFFFAOYSA-N 0.000 description 1
- BXRFQSNOROATLV-UHFFFAOYSA-N 4-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=C(C=O)C=C1 BXRFQSNOROATLV-UHFFFAOYSA-N 0.000 description 1
- OTLNPYWUJOZPPA-UHFFFAOYSA-N 4-nitrobenzoic acid Chemical compound OC(=O)C1=CC=C([N+]([O-])=O)C=C1 OTLNPYWUJOZPPA-UHFFFAOYSA-N 0.000 description 1
- 206010007269 Carcinogenicity Diseases 0.000 description 1
- DQFBYFPFKXHELB-UHFFFAOYSA-N Chalcone Natural products C=1C=CC=CC=1C(=O)C=CC1=CC=CC=C1 DQFBYFPFKXHELB-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 238000005579 Julia olefination reaction Methods 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 238000006845 Michael addition reaction Methods 0.000 description 1
- VVBXKASDRZXWON-UHFFFAOYSA-N N=[PH3] Chemical compound N=[PH3] VVBXKASDRZXWON-UHFFFAOYSA-N 0.000 description 1
- 238000003527 Peterson olefination reaction Methods 0.000 description 1
- 238000004639 Schlenk technique Methods 0.000 description 1
- 238000003800 Staudinger reaction Methods 0.000 description 1
- 238000007301 Vedej hydroxylation reaction Methods 0.000 description 1
- 238000007295 Wittig olefination reaction Methods 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 150000001347 alkyl bromides Chemical group 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 229940058905 antimony compound for treatment of leishmaniasis and trypanosomiasis Drugs 0.000 description 1
- 150000001463 antimony compounds Chemical class 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- RBFQJDQYXXHULB-UHFFFAOYSA-N arsane Chemical compound [AsH3] RBFQJDQYXXHULB-UHFFFAOYSA-N 0.000 description 1
- 238000005447 aza-Wittig reaction Methods 0.000 description 1
- XCQFGJYVKKCUFX-UHFFFAOYSA-N benzyl 4-nitrobenzoate Chemical compound C1=CC([N+](=O)[O-])=CC=C1C(=O)OCC1=CC=CC=C1 XCQFGJYVKKCUFX-UHFFFAOYSA-N 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 229960003237 betaine Drugs 0.000 description 1
- NHYXMAKLBXBVEO-UHFFFAOYSA-N bromomethyl acetate Chemical compound CC(=O)OCBr NHYXMAKLBXBVEO-UHFFFAOYSA-N 0.000 description 1
- 150000001728 carbonyl compounds Chemical class 0.000 description 1
- 231100000260 carcinogenicity Toxicity 0.000 description 1
- 230000007670 carcinogenicity Effects 0.000 description 1
- 235000005513 chalcones Nutrition 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000011944 chemoselective reduction Methods 0.000 description 1
- 238000011097 chromatography purification Methods 0.000 description 1
- 229940117916 cinnamic aldehyde Drugs 0.000 description 1
- KJPRLNWUNMBNBZ-UHFFFAOYSA-N cinnamic aldehyde Natural products O=CC=CC1=CC=CC=C1 KJPRLNWUNMBNBZ-UHFFFAOYSA-N 0.000 description 1
- 239000013065 commercial product Substances 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 238000006880 cross-coupling reaction Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 238000003795 desorption Methods 0.000 description 1
- 239000011903 deuterated solvents Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical class C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000005265 energy consumption Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 235000019439 ethyl acetate Nutrition 0.000 description 1
- WBJINCZRORDGAQ-UHFFFAOYSA-N ethyl formate Chemical compound CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 150000004795 grignard reagents Chemical class 0.000 description 1
- 239000003673 groundwater Substances 0.000 description 1
- 231100000086 high toxicity Toxicity 0.000 description 1
- 238000007871 hydride transfer reaction Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000006459 hydrosilylation reaction Methods 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 239000012948 isocyanate Substances 0.000 description 1
- 150000002513 isocyanates Chemical class 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- SKTCDJAMAYNROS-UHFFFAOYSA-N methoxycyclopentane Chemical compound COC1CCCC1 SKTCDJAMAYNROS-UHFFFAOYSA-N 0.000 description 1
- ACEONLNNWKIPTM-UHFFFAOYSA-N methyl 2-bromopropanoate Chemical compound COC(=O)C(C)Br ACEONLNNWKIPTM-UHFFFAOYSA-N 0.000 description 1
- NLWBJPPMPLPZIE-UHFFFAOYSA-N methyl 4-(bromomethyl)benzoate Chemical compound COC(=O)C1=CC=C(CBr)C=C1 NLWBJPPMPLPZIE-UHFFFAOYSA-N 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 229910052750 molybdenum Inorganic materials 0.000 description 1
- PYLWMHQQBFSUBP-UHFFFAOYSA-N monofluorobenzene Chemical compound FC1=CC=CC=C1 PYLWMHQQBFSUBP-UHFFFAOYSA-N 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- HGBOYTHUEUWSSQ-UHFFFAOYSA-N pentanal Chemical compound CCCCC=O HGBOYTHUEUWSSQ-UHFFFAOYSA-N 0.000 description 1
- LIGACIXOYTUXAW-UHFFFAOYSA-N phenacyl bromide Chemical compound BrCC(=O)C1=CC=CC=C1 LIGACIXOYTUXAW-UHFFFAOYSA-N 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- DHRLEVQXOMLTIM-UHFFFAOYSA-N phosphoric acid;trioxomolybdenum Chemical compound O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.OP(O)(O)=O DHRLEVQXOMLTIM-UHFFFAOYSA-N 0.000 description 1
- OJMIONKXNSYLSR-UHFFFAOYSA-N phosphorous acid Chemical compound OP(O)O OJMIONKXNSYLSR-UHFFFAOYSA-N 0.000 description 1
- 238000001394 phosphorus-31 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000012286 potassium permanganate Substances 0.000 description 1
- 150000003138 primary alcohols Chemical class 0.000 description 1
- VVWRJUBEIPHGQF-MDZDMXLPSA-N propan-2-yl (ne)-n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)\N=N\C(=O)OC(C)C VVWRJUBEIPHGQF-MDZDMXLPSA-N 0.000 description 1
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000006798 ring closing metathesis reaction Methods 0.000 description 1
- 229910052707 ruthenium Inorganic materials 0.000 description 1
- 150000003333 secondary alcohols Chemical class 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000011734 sodium Substances 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
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 150000001629 stilbenes Chemical class 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- XSOKHXFFCGXDJZ-UHFFFAOYSA-N telluride(2-) Chemical compound [Te-2] XSOKHXFFCGXDJZ-UHFFFAOYSA-N 0.000 description 1
- 150000003568 thioethers Chemical class 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- ROBPXJWVYLAUFL-UHFFFAOYSA-N trichlorosilylamine Chemical compound N[Si](Cl)(Cl)Cl ROBPXJWVYLAUFL-UHFFFAOYSA-N 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
Classifications
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- C07C1/32—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon starting from compounds containing hetero-atoms other than or in addition to oxygen or halogen
- C07C1/34—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon starting from compounds containing hetero-atoms other than or in addition to oxygen or halogen reacting phosphines with aldehydes or ketones, e.g. Wittig reaction
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Description
本出願は、2009年4月6日に出願の米国仮特許出願第61/167,101号に対して優先権を主張する。
炭素−炭素二重結合の形成は、多くの天然物及び薬品の製造にそれらの集合が必要であるために、現代の合成化学が基づく根幹の一つを表す。したがって、非常に多くの炭素−炭素二重結合の構築方法が発達してきた。直接脱離に加えて、アルケンの所定の形成に信頼性の高い4つの方法:ウィッティヒ反応、ペーターソン反応、及びコシェンスキー−ジュリアオレフィン化反応、ならびにメタセシスがある。現在、メタセシスのみが触媒的であり、そしてこれはアルケン出発物質を要し、適切に結合した遷移金属触媒(通常Ru又はMo)の高い負荷を伴って限定されるが、しばしば必要とされ、そして閉環メタセシスの場合、高希釈を要する。遷移金属の使用は、例えば活性な薬剤として使用される目的のあらゆる製品のために、いかなる遷移金属も除去されるか又は実質的に還元されなければならない点で複雑な事態を招きうる。
本発明は、ホスフィンを使用する触媒的ウィッティヒ方法に関する。この方法は、反応体及びアルデヒド、ケトン、又はエステルからオレフィンを生成するために使用される。この方法は、ホスフィンオキシド前触媒(precatalyst)を供給し、そしてホスフィンオキシド前触媒を還元して、ホスフィンを生成する工程を含む。次にホスフィン及び反応体からホスホニウムイリド前駆体を形成し、そして次にホスホニウムイリド前駆体からホスホニウムイリドを生成する。このホスホニウムイリドをアルデヒド、ケトン、又はエステルと反応させて、オレフィン及びホスフィンオキシドを形成する。次にホスフィンオキシドによりサイクルに再び入る。
図3は、提案されている触媒的ウィッティヒ反応の概略図を示す。Aは、ホスホニウムイリド前駆体を、典型的には、ホスホニウム塩により形成することを示す。Bは、ホスホニウムイリドを、通常、脱プロトン化により生成することを示す。Cは、ホスフィンオキシドの同時生成を伴うオレフィン化を示す。Dは、ホスフィンオキシド副生成物を還元し、ホスフィンを生成して、触媒的サイクルに再び入ることを示す。
全ての試薬は、商業的供給源から購入し、そして特に記載のない限り、更に精製しないで使用した。乾燥ジメチルエーテル(DME)及びアセトニトリル(ACN)(4Åモレキュラーシーブで保存した)をFlukaから購入し、そしてアルゴン下で処理した。トルエンを水素化カルシウムから新たに蒸留し、そしてアルゴン下で処理した。重水素化溶媒をCambridge Isotope Laboratories, Inc.から購入した。薄層クロマトグラフィー(TLC)をSorbent Technologies Silica G w/UV 254 アルミニウム裏打ちプレートで行い、そしてスポットをUV光線(254nm)、過マンガン酸カリウム、又はリンモリブデン酸の染色を使用して可視化した。カラムクロマトグラフィー精製をSorbent Technologies 60(230×400メッシュ)のフラッシュ技術を使用して実施した。NMRスペクトルをJEOL ECX-300及びJEOL Eclipse+500分光計で記録した。1Hに関する化学シフト(δ)を、重水素化溶媒(CHCl3、δ 7.26ppm)の残留プロトンのシグナルを基準として、百万分率(ppm)で示す;結合定数をヘルツ(Hz)で表す。以下の略語を使用する:s=一重線、d=二重線、t=三重線、m=多重線、dd=二重線の二重線、dt=三重線の二重線、dq=四重線の二重線、q=四重線、そしてqn=五重線。ガスクロマトグラフィーをVarian Series GC/MS/MS 240 Systemで行い、そして記載される収率は、内部標準としてウンデカンのキャリブレーションエリアを基準とする。水素化をThalesNano(ハンガリー)製のH-Cube Midi(登録商標)で行った。全ての実験を、特に断りのない限り、Schlenkの技術を使用して乾燥アルゴン下で実施した。反応が非選択的である場合、化合物をEとZの混合物として単離した。E及びZは、反応の間に形成された結合の立体化学を表す。
化合物(1)の調製: 3−メチル−1−フェニルホスホラン−1−オキシド
市販の3−メチル−1−フェニル−2−ホスホレン−1−オキシド(3.0g、16mmol、CAS 707−61−9)を、500mL計量丸底フラスコにて空気中で迅速に計量した。メタノール(300mL)を加え、0.05M溶液を調製した。ホスホレンオキシドを、10% Pd/Cを含む触媒カートリッジを備えるH-Cube Midi(登録商標)により水素化した。還元がH2(20bar)下、周囲温度にて流速1mL/minで起こった。メタノールを真空で除去して、生成物をジアステレオマーの2:1粘性混合物として収率100%で得た。1H−NMR及び31P−NMRスペクトルは前述のデータと一致した。
一般手順を図6の最上部に概説する。撹拌子を備える1ドラムバイアルに、3−メチル−1−フェニルホスホラン−1−オキシド(1)(19mg、10mol%)及び塩基(1.5mmol、1.5当量)を空気中で入れた;アルデヒドが固体である場合、それをこの時点で加えた(1.0mmol、1.0当量)。次にバイアルをセプタムで密閉し、アルゴンでパージした。蒸留した溶媒(0.33mL)、シラン(1.1〜1.5mmol、1.1〜1.5当量)、オルガノハライド(1.1〜1.5mmol、1.1〜1.5当量)を加えた;アルデヒドが液体である場合、それをこの時点で加えた(1.0mmol、1.0当量)。セプタムを不活性雰囲気下でPTFEラインねじ蓋と代え、反応物を100℃で24時間加熱した。GC/MS分析を行わない場合、粗反応混合物をセライトの栓を通して濾過し、真空で濃縮し、フラッシュカラムクロマトグラフィーにより精製した。最大の収量を得るために反応物を激しく撹拌することが重要である。
本実施例によりホスフィンオキシド、3−メチル−フェニルホスホラン−1−オキシド(1)(図3の工程D)の還元に関する様々な条件を試験する。ジフェニルシランを項目1〜11及び13に関して使用し、フェニルシランを項目12及び14に関して使用した。アセトニトリル又はトルエンを溶媒として使用した。塩基を項目11〜14に加えた。表1に示すように、反応を様々な温度、様々な時間で行った。収率を1H−NMRでメチルシグナルの積分により測定した。
実行可能な触媒的ウィッティヒ方法に関して、ホスフィンオキシドは、十分な速度でホスフィンに還元されなければならない。クロスカップリング化学を触媒するパラジウムをガイドとして使用する場合、大部分の反応が24時間足らずで完了した。10mol%の触媒を使用した場合、定量的収率を達成するために10回循環することが必要である。上記のプロトコル設計パラメーターを想定すると、反応は24時間以内に完了しなければならない。したがって、プロトコル設計の制約に対応することを確実にするため、ホスフィンオキシドを約2.4時間以内に完全に還元しなければならない。ホスフィンオキシド 1を60℃及び100℃で10分間〜1時間の範囲の時間で試験した。10mol%の1を使用し、ジフェニルシラン1.2当量で使用した。図4a及び4bで示す結果は、ホスフィンオキシド還元の許容速度を保持するために、100℃の温度が必要であることを示す。
実施例3を、ホスホニウムイリドの生成、工程B(図3を参照)で使用する最良の塩基を評価するために実施した。条件は、実施例4と同様であった。反応をトルエン中で60℃にて18時間実施した。塩基を3当量で使用した。
ベンズアルデヒドのケイ皮酸メチルへの転換(図6の構造2)を4つの異なるシラン:フェニルシラン、ジフェニルシラン、トリフェニルシラン、及びトリメトキシシランを使用する触媒的方法で試みた。結果を表2に示す。ベンズアルデヒドを1.0mmolで、ブロモ酢酸メチルを1.3mmolで使用した。ホスフィンオキシド(1)を10mol%で使用した。シランを1.1mmolで、Na2CO3を1.5mmolで使用した。反応は、トルエン中100℃であった。収率をキャリブレーション内部標準(ウンデカン)に対してGC/MS/MSにより測定し、二重に行った。E/Z比をGC/MS/MSにより測定した。NDは、測定していないを意味する。
実施例5を最良の溶媒を決定するために実施した。実施例4と同様の条件を、表3に示されるような溶媒及び反応時間の変化を伴い使用した。ジフェニルシランを使用した。
溶媒及び温度の別の評価を実施例の条件を使用し、ジフェニルシランを用いて実施した。反応は、表4に示される温度で24時間であった。これらの条件下、溶媒及び温度を変化させることにより、収率に少しの変化が生じた。しかしながら、温度を80℃に下げることにより(項目3対4)、相当量のZ生成物をもたらした。これによりオレフィン化後の異性化現象、おそらくホスフィン媒介の現象を示唆する。この仮説に関する根拠を提供するために、Z−ケイ皮酸メチルを3−メチル−1−フェニルホスホラン−1−オキシド由来のホスフィンをも用いてd6−ベンゼン中で100℃にて処理した(密閉管)。E異性体への異性化の完了を観測した。トリメトキシシランを使用する時の選択的方法の欠如(表2、項目4)は、ホスフィン形成の不十分な速度に起因し、アルデヒド消費後の生成物の完全な異性化をもたらしうる。
我々は、前触媒充填の効果を収率及びE:Z比について評価した。実施例4と同様の条件を使用した。ジフェニルシランを1.1当量で使用した。
以下の化合物を、上記で概説した一般的な触媒的方法を使用して生成した。全ての生成物を1H−NMRにより検証した。それぞれの構造を図6に示す。反応を二重に行った。
反応は、トルエン中で85℃、90℃及び100℃にて24時間かけて、E−選択的である。我々は、これは、Z異性体へのホスフィンのMichael付加により起こると信じる。この機構を20mol%ホスフィンオキシド(1)を使用して、異性体的に純粋なZ−ケイ皮酸メチルを用いて80℃で24時間評価した。プロトンNMRは、この機構的経路を裏づける。
反応を図9に示す。撹拌子を備える1ドラムバイアルに、ホスフィンオキシド1(9.7mg、10mol%)、4−ニトロ安息香酸(51.7μL、0.5mmol)、及びジイソプロピルアゾジカルボキシラート(DIAD、147.5μL、0.75mmol)を空気中で入れた。次にバイアルをセプタムで密閉し、アルゴンでパージした。蒸留トルエン(1.5mL)を加えた。反応物を撹拌した。フェニルシラン(67.8μL、0.55mmol)、及びベンジルアルコール(51.7μL、0.5mmol)を加えた。セプタムを不活性雰囲気下でPTFEラインのねじ蓋と代え、反応物を80℃で24時間加熱した。粗反応混合物をセライトの栓を通して濾過し、真空で濃縮し、フラッシュクロマトグラフィーにより精製して、標記化合物、63%、81.0mgを得た。我々の知る限り、これはホスフィンにおける触媒的な光延反応の最初の実施例である。
撹拌子を備える1ドラムバイアルに、ホスフィンオキシド1(19mg、10mol%)、及びナトリウム tert−ブチルカルボナート(1.5mmol、1.5当量)を空気中で入れた。次にバイアルをセプタムで密閉し、アルゴンでパージした。蒸留トルエン(1.00mL)、ジフェニルシラン(1.2mmol、1.2当量)、及び臭化ベンジル(1.2mmol、1.2当量)を加えた。ベンズアルデヒド(1.0mmol、1.0当量)をシリンジによりゆっくりと5時間かけて加えた。反応物を100℃で20時間加熱した。スチルベンの収率は、合わせた収率82.91%に対して、(cis)28.86%及び(trans)54.05%であると測定した。1H−NMRスペクトルは、市販の化合物、cis−スチルベン(Alfa Aesar)、及びtrans−スチルベン(TCI)のスペクトルと一致した。
Claims (9)
- オルガノハライド及びアルデヒド、ケトン、又はエステルからオレフィンを形成する、触媒的ウィッティヒ方法であって、下記の工程:
a)オルガノハライド、アルデヒド、ケトン、又はエステル、ホスフィンオキシド、及び、シランを含む還元剤を供給すること;
b)還元剤でホスフィンオキシドを還元し、ホスフィンを生成すること;
c)ホスフィン及びオルガノハライドを用いてホスホニウムイリド前駆体を形成すること;
d)ホスホニウムイリド前駆体からホスホニウムイリドを生成すること;そして
e)ホスホニウムイリドをアルデヒド、ケトン、又はエステルと反応させて、オレフィン及び該ホスフィンオキシドを形成すること
を含む、方法。 - ホスホニウムイリド前駆体が、ホスホニウム塩である、請求項1記載の触媒的ウィッティヒ方法。
- ホスホニウムイリドが、脱プロトン化により生成される、請求項1記載の触媒的ウィッティヒ方法。
- 還元剤が、フェニルシラン、ジフェニルシラン、トリフェニルシラン、及びトリメトキシシランからなる群より選択される少なくとも一種を含む、請求項1記載の触媒的ウィッティヒ方法。
- 工程d)を塩基の存在下で行う、請求項1記載の触媒的ウィッティヒ方法。
- 塩基が、Na 2 CO 3 を含む、請求項5記載の触媒的ウィッティヒ方法。
- ホスフィンオキシドが、環状である、請求項1記載の触媒的ウィッティヒ方法。
- ホスフィンオキシドが、3−メチル−1−フェニルホスホラン−1−オキシドである、請求項1記載の触媒的ウィッティヒ方法。
- 条件が、E又はZ異性体を選択的に得るために選択される、請求項1記載の触媒的ウィッティヒ方法。
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