CN102438970B - 催化的维蒂希反应及光延反应 - Google Patents
催化的维蒂希反应及光延反应 Download PDFInfo
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- CN102438970B CN102438970B CN201080015027.8A CN201080015027A CN102438970B CN 102438970 B CN102438970 B CN 102438970B CN 201080015027 A CN201080015027 A CN 201080015027A CN 102438970 B CN102438970 B CN 102438970B
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- Prior art keywords
- phosphine
- reaction
- equivalents
- phosphine oxide
- silane
- Prior art date
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- 238000006555 catalytic reaction Methods 0.000 title claims abstract description 43
- 238000006243 chemical reaction Methods 0.000 title abstract description 58
- 238000007239 Wittig reaction Methods 0.000 title description 27
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims abstract description 111
- AUONHKJOIZSQGR-UHFFFAOYSA-N oxophosphane Chemical compound P=O AUONHKJOIZSQGR-UHFFFAOYSA-N 0.000 claims abstract description 68
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims abstract description 56
- 238000000034 method Methods 0.000 claims abstract description 43
- 229910052698 phosphorus Inorganic materials 0.000 claims abstract description 30
- 239000011574 phosphorus Substances 0.000 claims abstract description 30
- 230000002829 reductive effect Effects 0.000 claims abstract description 23
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims abstract description 22
- 150000001336 alkenes Chemical class 0.000 claims abstract description 22
- 150000001299 aldehydes Chemical class 0.000 claims abstract description 16
- 150000002148 esters Chemical class 0.000 claims abstract description 11
- 150000002576 ketones Chemical class 0.000 claims abstract description 10
- 150000002896 organic halogen compounds Chemical class 0.000 claims abstract description 7
- 150000003017 phosphorus Chemical class 0.000 claims abstract description 7
- VDCSGNNYCFPWFK-UHFFFAOYSA-N diphenylsilane Chemical compound C=1C=CC=CC=1[SiH2]C1=CC=CC=C1 VDCSGNNYCFPWFK-UHFFFAOYSA-N 0.000 claims description 33
- -1 3-methyl isophthalic acid-phenyl phospholane-1-oxide compound Chemical class 0.000 claims description 26
- 239000003513 alkali Substances 0.000 claims description 19
- 229910000077 silane Inorganic materials 0.000 claims description 15
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 claims description 14
- 239000003795 chemical substances by application Substances 0.000 claims description 9
- PARWUHTVGZSQPD-UHFFFAOYSA-N phenylsilane Chemical compound [SiH3]C1=CC=CC=C1 PARWUHTVGZSQPD-UHFFFAOYSA-N 0.000 claims description 9
- 239000003638 chemical reducing agent Substances 0.000 claims description 4
- 230000005595 deprotonation Effects 0.000 claims description 4
- 238000010537 deprotonation reaction Methods 0.000 claims description 4
- CUXQLKLUPGTTKL-UHFFFAOYSA-M microcosmic salt Chemical compound [NH4+].[Na+].OP([O-])([O-])=O CUXQLKLUPGTTKL-UHFFFAOYSA-M 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
- 239000002585 base Substances 0.000 claims description 3
- 150000003003 phosphines Chemical class 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims 2
- 125000003545 alkoxy group Chemical group 0.000 claims 1
- 125000003118 aryl group Chemical group 0.000 claims 1
- 125000001072 heteroaryl group Chemical group 0.000 claims 1
- 150000004756 silanes Chemical class 0.000 claims 1
- 239000003054 catalyst Substances 0.000 abstract description 12
- 239000012041 precatalyst Substances 0.000 abstract description 7
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 102
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 46
- UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Substances C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 46
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 35
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
- 238000006722 reduction reaction Methods 0.000 description 23
- 229910000029 sodium carbonate Inorganic materials 0.000 description 23
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- YDCHPLOFQATIDS-UHFFFAOYSA-N methyl 2-bromoacetate Chemical compound COC(=O)CBr YDCHPLOFQATIDS-UHFFFAOYSA-N 0.000 description 13
- 238000003786 synthesis reaction Methods 0.000 description 13
- 239000006227 byproduct Substances 0.000 description 12
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 10
- 239000007787 solid Substances 0.000 description 10
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- 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
- 239000007789 gas Substances 0.000 description 6
- 238000011068 loading method Methods 0.000 description 6
- 238000011160 research Methods 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
- 238000005481 NMR spectroscopy Methods 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- BAPJBEWLBFYGME-UHFFFAOYSA-N acrylic acid methyl ester Natural products COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 description 5
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- 238000013461 design Methods 0.000 description 5
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- CCRCUPLGCSFEDV-BQYQJAHWSA-N methyl trans-cinnamate Chemical compound COC(=O)\C=C\C1=CC=CC=C1 CCRCUPLGCSFEDV-BQYQJAHWSA-N 0.000 description 5
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- QILOUBBQVGUFNG-UHFFFAOYSA-N methyl 2-methyl-3-phenylprop-2-enoate Chemical class COC(=O)C(C)=CC1=CC=CC=C1 QILOUBBQVGUFNG-UHFFFAOYSA-N 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
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- VEBCSALPNMISTC-UHFFFAOYSA-N 3-cyclohexylprop-2-enenitrile Chemical compound N#CC=CC1CCCCC1 VEBCSALPNMISTC-UHFFFAOYSA-N 0.000 description 3
- YDFNNPKYXYTLOV-UHFFFAOYSA-N 5,9-dimethylundeca-2,8-dienenitrile Chemical compound CC(CC=CC#N)CCC=C(CC)C YDFNNPKYXYTLOV-UHFFFAOYSA-N 0.000 description 3
- NLHHRLWOUZZQLW-UHFFFAOYSA-N Acrylonitrile Chemical compound C=CC#N NLHHRLWOUZZQLW-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- QPJVMBTYPHYUOC-UHFFFAOYSA-N Methyl benzoate Natural products COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 3
- 229910052785 arsenic Inorganic materials 0.000 description 3
- RQNWIZPPADIBDY-UHFFFAOYSA-N arsenic atom Chemical compound [As] RQNWIZPPADIBDY-UHFFFAOYSA-N 0.000 description 3
- 239000012298 atmosphere Substances 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
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- 239000003153 chemical reaction reagent Substances 0.000 description 3
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- IQQDLHGWGKEQDS-UHFFFAOYSA-N methyl hept-2-enoate Chemical class CCCCC=CC(=O)OC IQQDLHGWGKEQDS-UHFFFAOYSA-N 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- MPQXHAGKBWFSNV-UHFFFAOYSA-N oxidophosphanium Chemical group [PH3]=O MPQXHAGKBWFSNV-UHFFFAOYSA-N 0.000 description 3
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- ZYEMNJWJLARYJR-UHFFFAOYSA-M sodium;tert-butyl carbonate Chemical compound [Na+].CC(C)(C)OC([O-])=O ZYEMNJWJLARYJR-UHFFFAOYSA-M 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 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 3
- BYQADQLDVPAGSR-UHFFFAOYSA-N toluene;hydrobromide Chemical compound Br.CC1=CC=CC=C1 BYQADQLDVPAGSR-UHFFFAOYSA-N 0.000 description 3
- 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 3
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- RSJKGSCJYJTIGS-UHFFFAOYSA-N undecane Chemical compound CCCCCCCCCCC RSJKGSCJYJTIGS-UHFFFAOYSA-N 0.000 description 3
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- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
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- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
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- ZNJMTZNUYPTNLN-UHFFFAOYSA-N methyl 3-(2,6-dichlorophenyl)prop-2-enoate Chemical class COC(=O)C=CC1=C(Cl)C=CC=C1Cl ZNJMTZNUYPTNLN-UHFFFAOYSA-N 0.000 description 2
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- 125000003232 p-nitrobenzoyl group Chemical group [N+](=O)([O-])C1=CC=C(C(=O)*)C=C1 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 230000037361 pathway Effects 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
- 150000004857 phospholes Chemical class 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
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 231100000572 poisoning Toxicity 0.000 description 1
- 230000000607 poisoning effect Effects 0.000 description 1
- 230000007096 poisonous effect Effects 0.000 description 1
- 239000012286 potassium permanganate Substances 0.000 description 1
- 238000003822 preparative gas chromatography Methods 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000010223 real-time analysis Methods 0.000 description 1
- 238000012552 review Methods 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
- 239000012265 solid product Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000004575 stone Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- XSOKHXFFCGXDJZ-UHFFFAOYSA-N telluride(2-) Chemical compound [Te-2] XSOKHXFFCGXDJZ-UHFFFAOYSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 150000003568 thioethers Chemical class 0.000 description 1
- ROBPXJWVYLAUFL-UHFFFAOYSA-N trichlorosilylamine Chemical compound N[Si](Cl)(Cl)Cl ROBPXJWVYLAUFL-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
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Abstract
本发明提供一种采用膦的催化的维蒂希方法,其包含以下步骤:提供氧化膦预催化剂,并使该氧化膦预催化剂还原以产生膦;由膦与有机卤化物形成磷叶立德前驱体;由该磷叶立德前驱体产生磷叶立德;使该磷叶立德前驱体与醛、酮或酯反应以形成烯烃及其后可再次进入循环的氧化膦。本发明也针对以膦催化的光延反应。
Description
技术领域
本发明涉及一种采用膦的催化的维蒂希方法。
背景技术
碳-碳双键的形成代表近代合成化学的基石之一,其原因在于多数天然产物与药物的制造需与其组合。结果,便开发有多种用于建构碳-碳双键的程序。除了直接的消去反应之外,现今已有四种可靠的方法供烯类的日常形成:维蒂希、皮特森(Peterson)、Kocienski-Julia烯烃合成、以及复分解反应。目前,仅有复分解反应为催化性,甚而其仍受限于需要烯类起始材料、时常需要有高装载量的经适当错合的过渡金属催化剂,通常为钌或钼,而且在进行闭环复分解反应时需要高稀释度。使用过渡金属可能使程序复杂化,其中在于必须对任何拟用作例如活性医药试剂的产物,将过渡金属移除或实质上予以还原。
此外,就化学合成路径的选择而言,环保意识逐渐影响决策的制定,其中该选择是受特殊程序的废弃物与耗能模式所影响。例如,作为最被广泛采用的烯烃合成程序的维蒂希反应,其付出了代价:依化学计量形成了副产物氧化膦。
因此,便极需开发可限制废弃物的产生、或减少所制造例如有毒至有害的废弃物的新颖且环保的催化方法。有机催化程序的成功设计与实施能够减少化学工业对其环境生态所产生的碳足迹。因此,可选择性地建构烯烃的有机催化方法便代表着重要的进展。
上述三种化学计量烯烃合成程序当中,实际上可由化学计量程序转移至催化程序,同时选择性地形成E-或Z-烯类的唯一程序为维蒂希反应。维蒂希反应是在1953年由格奥尔格·维蒂希所发现,其涉及使醛或酮与磷叶立德反应,如此便产生随附的烯类与一般的氧化膦。维蒂希在此领域的先驱研究使其在1979年获得诺贝尔化学奖。由此发现起,维蒂希反应便被广泛使用,而此可由其被包含于多种天然产物的合成,以及本科生的实验室课程与教学内容中来证实。
图1说明以往教科书对维蒂希反应的图示说明。公认的机制涉及磷叶立德攻击醛或酮而产生氧膦烷中间体。氧膦烷的形成可经由磷叶立德与羰基化合物之间直接的[2+2]环加成反应来发生。此外,又提出首先形成偶极中间体(betaine intermediate),接着氧膦烷中间体经由逆[2+2]环加成反应崩解,而产生所要的随附的烯类与副产物氧化膦。维蒂希反应的进一步探讨可见于O'Brine et al.,Angew.Chem.Int.Ed.2009,48,6836-6839与其中所引用的参考文献。
虽然已有直接针对维蒂希反应的开发的显著成果,但严重的问题依旧存在且尚待解决。第一,该程序为化学计量;第二,副产物氧化膦的完全移除最耗时,或是无法达成。有时候,维蒂希反应会产生非镜相异构性混合物而须进行纯化。催化方案可减少副产物氧化膦的量。缺乏催化方案亦会排除掉重要的条件:由改变膦的结构来控制烯烃合成的可能性。如此较为不理想,因已显示出膦的结构会对反应的立体化学结果造成实质上的影响,因此,详细设计的膦便可达成选择性程序。
明白这点,催化的维蒂希反应的开发的障碍是难以克服的,而且催化程序的成功建构是取决于以下四个步骤是否完成:(A)形成磷叶立德前驱体(典型上为磷盐);(B)形成磷叶立德,一般是通过去质子化:(C)进行烯烃合成并伴随氧化膦的产生;及(D)使副产物氧化膦还原产生膦,而再次进入催化循环中。所述程序中最困难的是步骤D:其要求在醛或酮起始材料与烯类产物的存在下,使副产物氧化膦化学选择性地还原成膦。
一般可将磷由砷、碲、锑取代来改进此化学选择性还原反应的问题,因其所对应的氧化物明显较为容易还原,而此归因于键强度。实际上,所述方法可成功开发出采用胂、碲化物的催化的维蒂希型程序(对催化的醛类烯烃合成的评论,见F.E.Kuhn,A.M.Santos,Mini-Rev.Org.Chem.2004,1,55-64)。不佳地,广泛采用前述方法的严重缺点在于砷、碲与锑化合物的本质上的高毒性及致癌性;这些反应若以大规模进行,则特别是地下水的环境污染将会成为问题之一。重要的是,膦的催化用途并未遭遇到这些问题,因此以膦催化的维蒂希反应便可展现更广泛的使用性。再者,此可在没有会干扰过渡金属催化程序的中毒问题之下,结合维蒂希烯烃合成方案的效率与催化反应的合成效果。
此前述氧化膦至膦的还原反应对任何催化的维蒂希反应的成功开发而言是关键性的,因此,可使此还原反应发生作用的有效方法便有其详细探讨的价值。若追溯使氧化膦还原成膦的最优选的试剂类别则为硅烷。虽存在其它方法,但皆未有硅烷的前瞻性与可靠性。Fritzsche与其同事首先在1964年报导氧化膦与硅烷的还原反应(Fritzsche,H.et al.,“五价磷有机物至膦的还原:I.三级氧化膦于硅烷下至三级膦的还原”,Chem.Ber.1964,97,1988-1993;Fritzsche,H.et al.,“具有五价磷的有机物至膦的还原:II.三级氧化膦于三氯硅烷下至三级膦的还原”,Chem.Ber.1965,98,171-174;Fritzsche,H.et al.,“五价磷有机物至膦的还原:III.以硅烷制备一级与二级膦”,Chem.Ber.1965,98,1681-1687)。
这些著作对硅烷还原剂及所揭露的四种成效良好的还原剂-苯基硅烷、二苯基硅烷、三苯基硅烷及三氯硅烷进行了全面性的评价。归因于Fritzscge的成果,显示出苯基硅烷与三氯硅烷中最广泛与后者使用,且时常与最常被采用的胺碱并用。
还原的机制因硅烷而异,若为三氯硅烷时,在胺类的存在下常会导致中心磷的反转,而为苯基硅烷时则可保留状态,同时达成还原反应。
致力开发维蒂希反应中的催化程序时,主要是着眼于两个主要领域:(1)催化性地产生磷叶立德;(2)由砷取代磷,原因在于砷-氧键较相似的磷-氧键更容易形成。然而,其均未表示实际的催化的维蒂希反应,因其需催化性地使用膦。事实上,催化性的膦其仅有的记载用途是以相关的氮杂维蒂希反应揭露;然而,还原方案、异氰酸酯并无法使用于原始的反应中。因此,膦为催化性物种的催化的维蒂希反应的开发仍尚未达成。
光延反应在将一级与二级醇转换为酯、苯基醚、硫醚与各种其它化合物时也使用膦。其一般机制示于图7。该反应在1967年由OyoMitsunobu教授所发现,归因于其前瞻性、立体特异性、温和的反应条件,而被广泛使用于学术与工业实验室中。与维蒂希反应相似的光延反应是采用膦,并产生氧化膦作为副产物。与维蒂希反应相似,光延反应也常遭遇到产物分离与纯化相关的问题,而这些问题则是起因于副产物氧化膦与肼的形成。
有三种可能的方式可使光延反应为催化性:膦、肼及两者。图8说明以膦催化的光延反应循环。拟开发的最有挑战性的方案为需在同一烧瓶中存有还原剂(氧化膦至膦)与氧化剂(肼至偶氮化合物)竞争性催化方案。
发明内容
本发明针对采用膦的催化的维蒂希方法。该方法用于由有机卤化物与醛、酮或酯来产生烯烃。该方法包括提供氧化膦预催化剂与使氧化膦预催化剂还原而产生膦的步骤。其后,磷叶立德前驱体由膦与有机卤化物形成,接着磷叶立德则由磷叶立德前驱体产生。使此磷叶立德与醛、酮或酯反应而形成烯烃与氧化膦,随后氧化膦便再次进入循环中。
该方法显示以低至4mol%的氧化膦预催化剂的装载量可得高产率,而这些产率可与过渡金属催化方案相比较。开发耐用、有效、容易使用、具催化性的维蒂希方案将会对合成界产生深远的影响。所述程序可广泛采用于全世界的学术与工业实验室。
本发明也针对以膦催化的光延反应。
本发明进一步针对使在使用膦的反应中产生的氧化膦产物再循环的方法。该方法涉及使氧化膦还原成膦。
附图说明
图1说明维蒂希反应的机制;
图2说明所提出的催化的维蒂希反应的循环;
图3说明本发明实际的催化的维蒂希反应循环;
图4a与图4b说明使氧化膦在60℃与100℃下还原的研究结果;
图5说明碱的选择对反应的影响的研究结果;
图6说明以上段落中的一般催化反应,并显示根据本发明的催化反应所产生的各种产物的结构;
图7说明光延反应;
图8说明所提出的一般的催化的光延方法;
图9说明催化的光延反应;以及
图10说明所提出的氧化膦结构。
具体实施方式
图3显示所提出的催化的维蒂希反应的简图。A表示磷叶立德前驱体的形成,典型上是通过一磷盐。B表示磷叶立德的产生,一般是通过去质子化。C表示烯烃合成,并伴随氧化膦的产生。D表示的副产物氧化膦的还原,其产生膦而再次进入催化循环中。
针对催化的维蒂希反应的初始研究其目标在于所提出的催化循环中的每个步骤的系统性评价。使用氧化膦而非膦,来排除解读结果时的歧义性。产物的产生清楚地显示达成催化循环所需的步骤已完成。
氧化膦的使用要求循环中的第一步骤为还原成膦。如前述,有数种使氧化膦还原的可靠方法;其皆在有或无胺碱的存在下,大多使用强还原剂如氢化锂铝或三氯硅烷。所有前述方案均不適合整个催化循环-氢化锂铝使多数含羰基化合物还原,而三氯硅烷则使氧化膦还原,且一般伴有反转。虽有使用三氯硅烷-胺类混合物可保留立体化学的报导,但报导为光学纯度是基于保留程度,且经常不可靠。本发明人等不欲冒着发生反转的风险,原因在于伴有立体完整性的损失的还原反应会明显阻碍可经立体控制的催化的维蒂希方案的达成。此外,胺碱可能会在一般反应条件下使卤化物四级化。一般而言,氢化物转移至磷的难易度是随着苯基取代数的增加而降低。可预料在醛或酮的存在下使用硅烷会化学选择性地使氧化膦还原;可假设硅氢化反应未发生,原因在于其正常需要过渡金属催化剂。为确保适当的反应速率,本发明人等采用3-甲基-1-苯基磷杂环戊烷-1-氧化物,而非三苯基膦氧化物来作为氧化膦,原因在于前者较容易被还原。采用3-甲基-1-苯基磷杂环戊烷-1-氧化物的进一步优点在于其合成可在气流氢化条件下,由市售3-甲基-1-苯基-2-磷杂环戊烯-1-氧化物以2∶1的非镜相异构性混合物来迅速完成。
取得氧化膦3-甲基-1-苯基-2-磷杂环戊烯-1-氧化物后,本发明人等便着手进行所提出的循环中的两个关键步骤的评价;即,(D)氧化膦至膦的还原及(B)影响有效的叶立德形成所需的碱的优化。
氧化膦与还原性硅烷的组合也使用于光延反应中(图7)。本发明人等可使用氧化膦3-甲基-1-苯基-2-磷杂环戊烯-1-氧化物,以及作为还原剂的苯基硅烷来得到所要的产物。就本发明人等所知,此为以膦催化的光延反应的首次实例。
还原剂可选自苯基硅烷、二苯基硅烷、三苯基硅烷及三甲氧基硅烷。原则上可使用其他还原剂,但其须以可接受的速率使氧化膦还原,且未干扰羰基起始材料或烯类产物。优选还原剂为苯基硅烷或二苯基硅烷。
磷叶立德的有效去质子化必然会影响产物的形成。明白磷盐的pKa(酸度系数)为8-5左右,本发明人等便着手对碱进行评价。在弱碱的存在下尝试进行还原,以模拟可能的反应条件。碳酸钠可提供良好的产率并补充还原研究的内容,因此被选来探讨反应参数。其他有用的碱为碳酸叔丁酯钠(sodium tert-butyl carbonate)。惟,可使用任何各式各样的碱,原则上只要未干扰还原剂,则可使用任何碱。本发明人可使用二异丙基乙基胺(Hünig碱)及微波条件来达成反应。
对数种溶剂进行评价。已证明甲苯为最佳溶剂,乙腈虽可提供良好的产率,但因其沸点而使得应用受限。本发明人在本研究中多数使用甲苯,但可使用任何数量的溶剂如,例如1,2-二氯乙烷、环戊基甲基醚、氟苯、1,4-二恶烷及氯苯。
虽然在实例中将3-甲基-1-苯基-2-磷杂环戊烯-1-氧化物用作氧化膦,但其他氧化膦亦可有潜力地使用于催化的维蒂希方法与光延方法。对膦进行适当设计可达到更佳的立体控制。优选具有扭转环状结构的膦,因其可进行还原及翻转(因过渡状态下的立体拥挤而使得环状膦较容易还原)。图10说明某些所提出的氧化膦结构。类型I的氧化膦可通过由Vedejs所详细探讨、其后由Hoge与Tang使用,并涉及使用磷化锂阴离子的方法来快速获得。类型II的氧化物可由对应的磷酸,通过将其转换成氯化物并与格里纳试剂反应来迅速制得。类型III及IV的氧化膦可分别由如Kashman与Mügge所揭露的内容来产生。见Krech et al.,.Z Anorg.Allg.Chem.2003,629,1745-1746;及Minge et al.,Oraganometallics2001,21,680-684。
虽然特别针对维蒂希反应与光延反应而于此对本发明进行叙述,但应理解本发明具有更广的可应用性。可采用本发明的方法,而用于任何使用膦并产生副产物氧化膦的反应中。副产物氧化膦可被还原成膦,并可再次进入反应循环中。例如在施陶丁格反应中,迭氮化物与膦或亚磷酸盐的组合可产生亚氨基膦中间体。与氮杂叶立德的水解结合而产生氧化膦与胺类,此反应为一种将迭氮化物还原成胺的温和方法。三苯基膦一般用作还原剂,除胺类以外还产生三苯基膦氧化物作为副产物。
以下实例是用于进一步说明本发明,以对本领域技术人员提供完整的揭露和叙述,使其明白此处权利要求中的化合物、组成物、物件、装置及/或方法是如何產生和评价的,并未意图限制本发明的范围。在实例中,除非明确说明,否则量及百分比是依据重量,温度是以℃表示或为环境温度,而压力是在大气下或近似大气。
一般性实验
除非说明,否则所有试剂皆购自市售来源,并在未经进一步纯化的情况下使用。干燥二甲醚(DME)和乙腈(ACN)(储存于分子筛上方)是购自Fluka并在氩气下使用;氘化溶剂是购自Cambridge IsotopeLaboratories,Inc.。在Sorbent Technologies Silica G w/UV254背面涂布铝的平板上实施薄层色谱法(TLC),并使用紫外光(254nm)、高锰酸钾或磷钼酸染剂来使斑点显色;在Sorbent Technologies60(230×400筛目)使用快速分析技术来实施管柱色谱纯化。核磁共振(NMR)光谱记录于JEOL ECX-300与JEOL Eclipse+500光谱仪。1H的化学位移(6)以依据氘化溶剂(位于δ7.26ppm的CH3Cl)的残余质子信号的百万分之一(ppm)来指定;耦合常数则以赫兹(Hz)表示。使用以下缩写:s=单重态,d=双重态,t=三重态,m=多重态,dd=双重态的双重态,dt=三重态的双重态,dq=四重态的双重态,q=四重态及qn=五重态。在VarianSeries GC/MS/MS实施气相色谱法,且所报导的产率是基于整个作为内标准的十一烷的校正面积。在匈牙利ThalesNano制造的H-Cube Midi(商标)进行氢化反应。除非注明,否则所有的实验皆是在干燥氩气环境下使用希莱克技术(Schlenk technique)来进行。若反应为非选择性,则化合物分离为E与Z的混合物。E与Z指的是反应过程中所形成的键的立体化学。
合成步骤
化合物(1):3-甲基-1-苯基磷杂环戊烷-1-氧化物的制备
快速在空气中,在减去重量后的500mL圆底烧瓶中将市售3-甲基-1-苯基-2-磷杂环戊烯-1-氧化物(3.0g,16mmol,CAS707-61-9)秤重。添加甲醇(300mL)来制备0.05M溶液。通过具备含有10%铂/碳的触媒匣的H-Cube Midi(商标)使磷杂环戊烯氧化物氢化。还原反应在周围温度、氢气20bar、流率1mL/min下发生。在真空中除去甲醇而产获得产物,该产物为具黏性的非镜像异构物的2∶1混合物,产率为100%。1H-NMR及31P-NMR符合先前报导的数据。
化合物2~19的制备
其一般步骤概述于图6上方。将3-甲基-1-苯基磷杂环戊烷-1-氧化物(1)(19mg,10mol%)、碱(1.5mmol,1.5当量)装入装配有搅拌棒的1打兰(dram)小瓶中;若醛为固体,则在此点(1.0mmol,1.0当量)添加。将小瓶以隔膜密封并以氩气冲净。添加蒸馏溶剂(0.33mL)、硅烷(1.1~1.5mmol,1.1~1.5当量)与有机卤化物(1.1~1.5mmol,1.1~1.5当量);若醛为液体,则在此点(1.0mmol,1.0当量)添加。在钝气环境下,将隔膜由聚四氟乙烯衬里螺旋盖取代,并于100℃下对反应进行加热24小时。当未进行气相色谱-质谱(GC/MS)分析时,通过硅藻土制塞过滤粗制反应混合物,在真空中浓缩并通过快速管柱色谱法纯化。重要的是需对反应强力进行搅拌,以达最大产率。
气相色谱-质谱分析条件:按照一般性步骤,通过注射器注射正十一烷(GC/MS内标准,100μL/mmol醛)。使反应混合物通过硅胶短垫并由GC/MS/MS Varian240进行分析。
例1:氧化膦的还原研究
此例探讨氧化膦3-甲基-1-苯基磷杂环戊烷-1-氧化物(1)的各种用于还原的条件(图3中的步骤D)。对表列值1~11及13使用二苯基硅烷,对表列值12及14使用苯基硅烷。将乙腈或甲苯用作溶剂;表列值11~14添加有碱。如表1所示,在各种温度下以各种时间来进行反应。产
率是通过将1H-NMR中的甲基信号积分来决定。
[表1]
表列值10与13显示最佳产率,然而选择甲苯作为溶剂使用,原因在于乙腈有沸点较低之虞。碱的存在确实对结果造成了影响(见表列值8对11)。
例2:二次氧化膦的还原研究
为达可行的维蒂希程序,则氧化膦必须以足够的速率被还原/回收为膦。若使用钯催化交叉耦合化学反应作为导引,则多数反应可于24小时内完成。若本发明人等使用10mol%的催化剂装载量,则需循环10次以达定量产率。假设上述方案设计参数,且反应必须在24小时内完成。因此氧化膦必须在2.4小时或小于2.4小时内完全还原,以确保可符合方案设计的限制。在60℃与100℃下、10分钟至1小时的时间范围对氧化膦1的还原反应进行测试。使用10mol%的1,并使用1.2当量的二苯基硅烷。图4a与图4b中所说明的结果显示需要100℃的温度以保持可接受的氧化膦还原速率。
例3:碱的选择对反应的影响
进行例3来对用于步骤B-磷叶立德的产生(见图3)的最佳碱进行评价。条件与例4类似。反应在甲苯中、60℃下进行18小时;碱使用3当量。
结果示于图5。数种碱虽显示出高产率,惟碳酸钠可获得良好的产率,并且因其价廉且易于使用,而被选来进行进一步的研究。
例4:硅烷的选择对反应的影响
以使用四种不同硅烷-苯基硅烷、二苯基硅烷、三苯基硅烷及三甲氧基硅烷的催化程序来尝试进行苯甲醛至肉桂酸甲酯(图6的结构2)的转换,结果示于表2。使用苯甲醛1.0mmol、溴乙酸甲酯1.3mmol、氧化膦(1)10mol%、硅烷1.1mmol及Na2CO3(碳酸钠)1.5mmol。反应在甲苯中、100℃下进行。产率由相对校正后的内标准(十一烷)的GC/MS/MS来决定,并重复进行;E/Z比由GC/MS/MS来决定。ND表示未决定(notdetermined)。
[表2]
表列值 | 硅烷 | 产率(%) | 比(E∶Z) |
1 | Ph3SiH | 极微量 | ND |
2 | Ph2SiH2 | 75 | 1∶0 |
3 | PhSiH3 | 46 | 1∶0 |
4 | (MeO)3SiH | 61 | 5∶2 |
使用二苯基硅烷可产生高产率所要的肉桂酸甲酯。没有氧化膦的控制实验则未产生产物(未示出)。当表列值2的反应以4mol%的膦催化剂进行时,产率为73%。
例5:溶剂对反应的影响
进行例5来决定最佳溶剂。使用与例4相同的条件,如表3所示改变溶剂与反应时间,并使用二苯基硅烷。
[表3]
甲苯和乙腈可于24小时获得最佳产率,但乙腈因其沸点而使得应用受限。在具有各种介电常数的溶剂当中,约2∶1(E∶Z)的异构物比呈一致性。
例6:溶剂与温度的评价
使用例4的条件,以二苯基硅烷进行溶剂与温度的其它评价。在这些条件下,改变溶剂与温度产生了产率上的些微变化。然而,将温度减至80℃(表列值3对4)会获得显著量的Z产物,此提示后烯烃合成异构化过程可能是由膦催化。为对此假设提供证据,而在d6-苯、100℃下对Z-肉桂酸甲酯与由3-甲基-1-苯基磷杂环戊烷-1-氧化物衍生的膦实施处理(密封管)。可观察到完全异构化成E异构物。采用三甲氧基硅烷(表2的表列值4)时缺乏选择性程序可能缘自不充分的膦形成速率,而影响醛消耗后的完整异构化反应。
[表5]
表列值 | 溶剂 | 温度(℃) | 产率(%) | 比(E∶Z) |
1 | 二甲醚 | 100 | 50 | 1∶0 |
2 | 乙腈 | 100 | 52 | 1∶0 |
3 | 甲苯 | 100 | 60 | 1∶0 |
4 | 甲苯 | 80 | 62 | 2∶1 |
5 | 甲苯 | 70 | 49 | 2∶1 |
6 | 甲苯 | 60 | 33 | 2∶1 |
例7:预催化剂装载量的影响
评估预催化剂装载量对产率及E-Z比的影响。使用与例4相似的条件,并以1.1当量使用二苯基硅烷。
[表6]
表列值 | Mol% | 产率(%) | 比(E∶Z) |
1 | 4 | 70 | 1∶0 |
2 | 10 | 68 | 1∶0 |
3 | 20 | 80 | 1∶0 |
例8:受质的评价
使用以上概述的一般催化方法来制造以下化合物。所有产物均由1H-NMR来表征。其各个结构示于图6。所有反应均重复进行。
明显的结果在于杂环醛类可被采用,同时以高产率、非镜相控制(E/Z)产生5及7,并以高产率由香茅进行10与19的合成、及由对应的溴甲苯进行17与18的合成。如所预测,使用氯乙酸甲酯并未影响产率(68%对74%)。欲特别探讨的是能以高产率、适度的E/Z控制(产物8)来产生三取代烯类的烷基溴化物的使用。使用溴甲苯与溴乙腈时可能减少反应的选择性(比较产物3及18与产物2)。在这些情况下,膦的异构化途径可能明显减少或被阻断;选择性随后便可由上述维蒂希反应支配。亦说明催化的维蒂希方案来促进实用量的烯类的合成,如以4mol%装载量的1可产生3.39g的5(产率为67%)。这些结果可达成催化的膦控制立体选择性维蒂希反应的开发。
(E)-肉桂酸甲酯(2)是在甲苯(0.33mL)中、100℃下,使苯甲醛(100μL,1.0mmol,1.0当量)、溴乙酸甲酯(114μL,1.2mmol,1.2当量)、二苯基硅烷(200μL,1.1mmol,1.1当量)与碳酸钠(159mg,1.5mmol,1.5当量)反应24小时而获得。通过快速管柱色谱法(苯/戊烷,50∶50,Rf=0.25)纯化粗制产物,即得到白色固体产物(120mg,74%,E∶Z=1∶0)。光谱资料符合市售品(Aldrich)的光谱资料。以溴乙酸甲酯进行此反应时,分离产率为68%。
肉桂腈(3)是在甲苯(0.33mL)中、100℃下,使苯甲醛(100μL,1.0mmol,1.0当量)、溴乙腈(73μL,1.1mmol,1.1当量)、二苯基硅烷(200μL,1.1mmol,1.1当量)与碳酸钠(159mg,1.5mmol,1.5当量)反应24小时而获得。通过快速管柱色谱法(苯/戊烷,30∶70,Rf=0.11)纯化粗制产物,即得到无色油脂的(E)-3及(Z)-3(103mg,80%,E∶Z=3∶1)。
3-(2-噻吩基)丙烯腈(4)是在甲苯(0.33mL)中、100℃下,使2-噻吩甲醛(94μL,1.0mmol,1.0当量)、溴丙烯腈(73μL,1.1mmol,1.1当量)、二苯基硅烷(200μL,1.1mmol,1.1当量)与碳酸钠(159mg,1.5mmol,1.5当量)反应24小时而获得。通过快速管柱色谱法(苯/戊烷,50∶50,Rf=0.23)纯化粗制产物,即得到黄色油脂的4的异构混合物(100mg,74%,E∶Z=2∶1)。采用2当量(MeO)3SiH的单独反应可得85%的产率。
3-(2’-噻吩基)-(E)-丙烯酸甲酯(5)是在甲苯(0.33mL)中、100℃下,使2-噻吩甲醛(94μL,1.0mmol,1.0当量)、溴乙酸甲酯(100μL,1.1mmol,1.1当量)、二苯基硅烷(200μL,1.1mmol,1.1当量)与碳酸钠(159mg,1.5mmol,1.5当量)反应24小时而获得。通过快速管柱色谱法(苯/戊烷,50∶50,Rf=0.25)纯化粗制产物,即得到淡黄色固体的5(123mg,73%,E∶Z>95∶5)。酯5[c]是在甲苯(3.6mL)中,使上述醛类(1.0mL,10.7mmol,1.0当量)、溴乙酸甲酯(1.31mL,13.9mmol,1.3当量)、二苯基硅烷(23.7mL,12.8mmol,1.2当量)、碳酸钠(1.67g,16.0mmol,1.5当量)与1(207mg,0.10mmol,0.1当量)反应而获得。该反应是在钝气环境下、48mL压力容器中制备并于100℃下进行24小时,即得到标题化合物(1.13g,63%,E∶Z>95∶5)。酯5[d]是在甲苯(3.6mL)中,使上述醛类(2.81mL,30.0mmol,1.0当量)、溴乙酸甲酯(3.69mL,39.0mmol,1.3当量)、二苯基硅烷(6.70mL,36.2mmol,1.2当量)、碳酸钠(4.75g,44.8mmol,1.5当量)与1(233mg,0.04mmol,0.04当量)反应而获得。该反应是在钝气环境下、75mL压力容器中制备并于90℃下进行48小时,即得到标题化合物(3.9g,67%,E∶Z>95∶5)。
3-(4,-硝基苯基)-(E)-丙烯酸甲酯(6)是在甲苯(0.33mL)中、100℃下,使4-硝基苯甲醛(151mg,1.0mmol,1.0当量)、溴乙酸甲酯(100μL,1.1mmol,1.1当量)、二苯基硅烷(200μL,1.1mmol,1.1当量)与碳酸钠(159mg,1.5mmol,1.5当量)反应24小时而获得。通过快速管柱色谱法(乙酸乙酯/戊烷,20∶80,Rf=0.32)纯化粗制产物,即得到淡黄色固体的6(133mg,64%,E∶Z>95∶5)。
3-(4’-溴-2’-噻吩基)-(E)-丙烯酸甲酯(7)是在甲苯(0.33mL)中、100℃下,使4-溴噻吩-2-甲醛(191mg,1.0mmol,1.0当量)、溴乙酸甲酯(100μL,1.1mmol,1.1当量)、二苯基硅烷(200μL,1.1mmol,1.1当量)与碳酸钠(159mg,1.5mmol,1.5当量)反应24小时而获得。通过快速管柱色谱法(苯/戊烷,50∶50,Rf=0.20)纯化粗制产物,即得到黄色固体的7(173mg,70%,E∶Z>95∶5)。
2-甲基-3-苯基丙烯酸甲酯(8)是在甲苯(0.33mL)中、100℃下,使苯甲醛(100μL,1.0mmol,1.0当量)、2-溴丙酸甲酯(145μL,1.3mmol,1.3当量)、二苯基硅烷(225μL,1.2mmol,1.2当量)与碳酸钠(159mg,1.5mmol,1.5当量)反应24小时而获得。通过快速管柱色谱法(苯/戊烷,60∶40,E∶Rf=0.43,Z∶Rf=0.43)纯化粗制产物,即得到无色油脂的8(136mg,77%,E∶Z=5∶1)。
3-环己基丙烯腈(9)是在甲苯(0.33mL)中、100℃下,使环己烷甲醛(121μL,1.0mmol,1.0当量)、溴乙腈(91μL,1.3mmol,1.3当量)、二苯基硅烷(225μL,1.2mmol,1.2当量)与碳酸钠(159mg,1.5mmol,1.5当量)反应24小时而获得。通过快速管柱色谱法(醚/戊烷,1∶99,E∶Rf=0.09,Z∶Rf=0.14)纯化粗制产物,即得到皆呈无色油脂的(E)-9及(Z)-9(85mg,63%,E∶Z=2∶1)。
5,9-二甲基十一烷-2,8-二烯腈(10)是在甲苯(0.33mL)中、100℃下,使茅香(181μL,1.0mmol,1.0当量)、溴乙腈(98μL,1.4mmol,1.4当量)、二苯基硅烷(268μL,1.5mmol,1.5当量)与碳酸钠(159mg,1.5mmol,1.5当量)反应24小时而获得。通过快速管柱色谱法(苯/戊烷,20∶80,E∶Rf=0.16,Z∶Rf=0.20)纯化粗制产物,即得到皆呈黏性无色油脂的(Z)-10及(E)-10(117mg,66%,E∶Z=2∶1)。
(E)-3-邻甲苯基丙烯酸甲酯(11)是在甲苯(0.33mL)中、100℃下,使2-甲基苯甲醛(115μL,1.0mmol,1.0当量)、溴乙酸甲酯(125μL,1.3mmol,1.3当量)、二苯基硅烷(225μL,1.2mmol,1.2当量)与碳酸钠(159mg,1.5mmol,1.5当量)反应24小时而获得。通过快速管柱色谱法(苯/戊烷,40∶60,Rf=0.20)纯化粗制产物,即得到无色油脂的11(107mg,61%,E∶Z>95∶5)。
(E)-3-(4-(三氟甲基)苯基)丙烯酸甲酯(12)是在甲苯(0.33mL)中、100℃下,使4-(三氟甲基)苯甲醛(134μL,1.0mmol,1.0当量)、溴乙酸甲酯(125μL,1.3mmol,1.3当量)、二苯基硅烷(225μL,1.2mmol,1.2当量)与碳酸钠(159mg,1.5mmol,1.5当量)反应24小时而获得。通过快速管柱色谱法(苯/戊烷,35∶65,Rf=0.22)纯化粗制产物,即得到白色固体的12(186mg,81%,E∶Z>95∶5)。
查耳酮(13)是在甲苯(0.33mL)中、100℃下,使苯甲醛(100μL,1.0mmol,1.0当量)、2-溴苯乙酮(299mg,1.5mmol,1.5当量)、二苯基硅烷(190μL,1.1mmol,1.1当量)与二碳酸钠(126mg,1.5mmol,1.5当量)反应24小时而获得。通过快速管柱色谱法(苯/戊烷,35∶65,Rf=0.21)纯化粗制产物,即得到淡黄色固体的13(154mg,74%,E∶Z>95∶5)。
2-庚烯酸甲酯(14)是在甲苯(0.33mL)中、100℃下,使戊醛(106μL,1.0mmol,1.0当量)、溴乙酸甲酯(125μL,1.3mmol,1.3当量)、二苯基硅烷(225μL,1.2mmol,1.2当量)与碳酸钠(159mg,1.5mmol,1.5当量)反应24小时而获得。通过快速管柱色谱法(苯/戊烷,66.33,Rf=0.30)纯化粗制产物,即得到无色油脂的14(97mg,68%,E∶Z>95∶5)。
2,6-二氯肉桂酸甲酯(15)是在甲苯(0.33mL)中、100℃下,使2,6-二氯苯甲醛(175mg,1.0mmol,1.0当量)、溴乙酸甲酯(125μL,1.3mmol,1.3当量)、二苯基硅烷(225μL,1.2mmol,1.2当量)与碳酸钠(159mg,1.5mmol,1.5当量)反应24小时而获得。通过快速管柱色谱法(苯/戊烷,35∶65,E∶Rf=0.26,Z∶Rf=0.26)纯化粗制产物,即得到黏性无色油脂的15的异构混合物(178mg,77%,E∶Z=6∶1)。
5-苯基-2,4-戊二烯酸甲酯(16)是在甲苯(0.33mL)中、100℃下,使肉桂醛(126μL,1.0mmol,1.0当量)、溴乙酸甲酯(125μL,1.3mmol,1.3当量)、二苯基硅烷(225μL,1.2mmol,1.2当量)与碳酸钠(159mg,1.5mmol,1.5当量)反应24小时而获得。通过快速管柱色谱法(苯/戊烷,50∶50,E∶Rf=0.23,Z∶Rf=0.36)纯化粗制产物,即得到分别为白色固体及无色油脂的16的E及Z混合物(132mg,70%,E∶Z=5∶1)。次要的镜相异构物基于不同的耦合常数与已知的异构物的光谱来指定。
4-苯乙烯基苯甲酸甲酯(17)是在甲苯(0.33mL)中、100℃下,使苯甲醛(100μL,1.0mmol,1.0当量)、4-(溴甲基)苯甲酸甲酯(298mg,1.3mmol,1.3当量)、二苯基硅烷(225μL,1.2mmol,1.2当量)与碳酸钠(159mg,1.5mmol,1.5当量)反应24小时而获得。通过快速管柱色谱法(苯/戊烷,35∶65,E∶Rf=0.37,Z∶Rf=0.51)纯化粗制产物,即得到白色固体的(E)-17及无色油脂的(Z)-17(167mg,70%,E∶Z=3∶2)。
1-(4-三氟甲基苯基)-2-苯乙烯(18)是在甲苯(0.33mL)中、100℃下,使苯甲醛(100μL,1.0mmol,1.0当量)、4-(三氟甲基)溴甲苯(232μL,1.5mmol,1.5当量)、二苯基硅烷(230μL,1.2mmol,1.2当量)与碳酸钠(159mg,1.5mmol,1.5当量)反应24小时而获得。通过快速管柱色谱法(戊烷,100∶0,E∶Rf=0.42,Z∶Rf=0.55)纯化粗制产物,即得到白色固体的(E)-18及无色油脂的(Z)-18(174mg,70%,E∶Z=3∶2)。
(E)-5,9-二甲基十一烷-2,8-二烯酸甲酯(19)是在甲苯(0.33mL)中、100℃下,使茅香(180μL,1.0mmol,1.0当量)、溴乙腈(125μL,1.3mmol,1.3当量)、二苯基硅烷(225μL,1.2mmol,1.2当量)与碳酸钠(159mg,1.5mmol,1.5当量)反应24小时而获得。通过快速管柱色谱法(苯/戊烷,30∶70,Rf=0.17)纯化粗制产物,即得到无色油脂的19(137mg,65%,E∶Z>95∶5)。
例9:E-选择性维蒂希产物的形成机制的评估
该反应在甲苯中、85℃、90℃及100℃下超过24小时为E-选择性。兹认为这是通过膦至Z-异构物的麦克尔加成而发生。使用20mol%的氧化膦(1)、纯的异构物Z-肉桂酸甲酯,以80℃下24小时对此机制进行评估。氢核磁共振支持此机制途径。
例10:合成4-硝基苯甲酸苯酯的催化的光延方法
该反应说明于图9。在空气中,将氧化膦1(9.7mg,10mol%)、4-硝基苯甲酸(51.7μL,0.5mmol)与偶氮二甲酸二异丙酯(DIAD,147.5μL,0.75mmol)装入装配有搅拌棒的1打兰小瓶中。其后将小瓶以隔膜密封,并以氩气冲净。添加蒸馏甲苯(1.5mL),并将反应搅拌。添加苯基硅烷(67.8μL,0.55mmol)与苯甲醇(51.7μL,0.5mmol)。在钝气环境下,将隔膜由聚四氟乙烯衬里螺旋盖取代,并于80℃下对反应进行加热24小时。通过硅藻土制塞过滤粗制反应混合物,在真空中浓缩并通过快速管柱色谱法纯化,即产生标题化合物(63%,81.0mg)。就本发明人等所知,此为以膦催化的光延反应的首次实例。
例11:二苯乙烯的合成
在空气中,将氧化膦1(19mg,10mol%)与碳酸叔丁酯钠(1.5mmol,1.5当量)装入装配有搅拌棒的1打兰小瓶中。其后将小瓶以隔膜密封,并以氩气冲净。添加蒸馏甲苯(1.00mL)、二苯基硅烷(1.2mmol,1.2当量)与溴甲苯(1.2mmol,1.2当量)。以5小时,通过注射器缓缓添加苯甲醛(1.0mmol,1.0当量),并于100℃下对反应进行加热20小时。二苯乙烯的产率可决定为28.86%(顺式)与54.05%(反式),合并产率为82.91%。1H-NMR光谱符合市售化合物顺-二苯乙烯(Alfa Aesar)与反-二苯乙烯(TCI)的光谱。
本领域技术人员显然可由前述详细内容对本发明进行修饰与变更。所有修饰与变更均可由权利要求所包含。因此,将所有此处所引用的著作、专利及专利申请案整体并入以供参照。
Claims (11)
1.一种催化的维蒂希方法,其由一有机卤化物与醛、酮或酯来形成一烯烃,并包括以下步骤:
(a)提供i)该有机卤化物、ii)该醛、酮或酯、iii)一氧化膦与iv)一硅烷还原剂;
(b)以该硅烷还原剂使该氧化膦还原来产生膦;
(c)以该膦与有机卤化物形成一磷叶立德前驱体;
(d)由该磷叶立德前驱体产生一磷叶立德;及
(e)使该磷叶立德与该醛、酮或酯反应以形成该烯烃与所述氧化膦;
其中,在步骤(e)中产生的氧化膦进入步骤(b);
其中,该氧化膦从以下群组中选择:
其中,n在0与4之间;m在0与14之间;R是烷基;R1、R2、以及R3的每一个是烷基、芳基、烷氧基、或杂芳基。
2.根据权利要求1所述的催化的维蒂希方法,其特征在于,该磷叶立德前驱体为一磷盐。
3.根据权利要求1所述的催化的维蒂希方法,其特征在于,该磷叶立德通过去质子化来产生。
4.根据权利要求1所述的催化的维蒂希方法,其特征在于,该还原剂选自由苯基硅烷、二苯基硅烷、三苯基硅烷及三甲氧基硅烷所构成的群组。
5.根据权利要求1所述的催化的维蒂希方法,其特征在于,该还原剂选自由苯基硅烷及二苯基硅烷所构成的群组。
6.根据权利要求1所述的催化的维蒂希方法,其特征在于,步骤d在一碱的存在下进行。
7.根据权利要求6所述的催化的维蒂希方法,其特征在于,该碱包含一弱碱。
8.根据权利要求7所述的催化的维蒂希方法,其特征在于,该弱碱为Na2CO3。
9.根据权利要求1所述的催化的维蒂希方法,其特征在于,该氧化膦为环状。
10.根据权利要求1所述的催化的维蒂希方法,其特征在于,该氧化膦为3-甲基-1-苯基磷杂环戊烷-1-氧化物。
11.根据权利要求1所述的催化的维蒂希方法,其特征在于,选择条件来选择性地获得E或Z异构物。
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JPS51101924A (ja) * | 1975-03-06 | 1976-09-08 | Otsuka Pharma Co Ltd | Suchirenjudotainoseizoho |
US4131624A (en) * | 1977-07-05 | 1978-12-26 | M&T Chemicals Inc. | Reduction of phosphine oxides |
JPH01259010A (ja) | 1988-04-08 | 1989-10-16 | Kao Corp | ポリα,β−不飽和ニトリルの製造方法 |
JP3467307B2 (ja) | 1994-03-31 | 2003-11-17 | 信越化学工業株式会社 | ホスホニウム塩の製造方法 |
DE4443360A1 (de) * | 1994-12-06 | 1996-06-13 | Basf Ag | Verfahren zur reduktiven Deoxigenierung mittels eines Redoxkatalysators |
JP2008196004A (ja) * | 2007-02-13 | 2008-08-28 | Okayama Univ | トリアリールホスフィン誘導体の製造方法 |
-
2010
- 2010-04-06 EP EP10762310.0A patent/EP2417082B1/en not_active Not-in-force
- 2010-04-06 WO PCT/US2010/030112 patent/WO2010118042A2/en active Application Filing
- 2010-04-06 JP JP2012504783A patent/JP5689111B2/ja not_active Expired - Fee Related
- 2010-04-06 CN CN201080015027.8A patent/CN102438970B/zh not_active Expired - Fee Related
- 2010-04-06 US US13/263,224 patent/US8901365B2/en not_active Expired - Fee Related
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4751307A (en) * | 1985-01-17 | 1988-06-14 | Mallinckrodt, Inc. | Wittig-reaction processes |
EP0630877A1 (en) * | 1993-06-21 | 1994-12-28 | Shin-Etsu Chemical Co., Ltd. | Workup of Wittig reaction products |
CN1215723A (zh) * | 1997-10-03 | 1999-05-05 | 霍夫曼-拉罗奇有限公司 | 类胡萝卜素的制备方法 |
Non-Patent Citations (3)
Title |
---|
《用Witting反应合成三苯甲基取代烯烃》;凌莹等;《化学试剂》;20060215;第28卷(第2期);第111-112页 * |
On the Asymmetric Rh(Ⅰ) Catalyzed [4+2] Cycloisomerization Reaction. Electronic and Torsinal Ligangd Control of Absolute Stereoselection;Lydia McKinstry等;《Tetrahedron》;19941231;第50卷(第21期);第6151页倒数第8-14行 * |
The First Example of a Catalytic Wittig-Type Reaction. Tri-n-butylarsine-Catalyzed Olefination in the Presence of Trophenyl Phosphite;Lilan Shi等;《The Journal of Organic Chemistry》;19890428;第54卷(第9期);第2028页第1栏第3-13行以及SchemeⅡ,表1第2行 * |
Also Published As
Publication number | Publication date |
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CN102438970A (zh) | 2012-05-02 |
EP2417082B1 (en) | 2016-03-16 |
EP2417082A4 (en) | 2012-09-19 |
US8901365B2 (en) | 2014-12-02 |
JP5689111B2 (ja) | 2015-03-25 |
WO2010118042A2 (en) | 2010-10-14 |
US20120029211A1 (en) | 2012-02-02 |
EP2417082A2 (en) | 2012-02-15 |
WO2010118042A3 (en) | 2011-01-13 |
JP2012522845A (ja) | 2012-09-27 |
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