CN114085250A - 一种含Ugi’s胺砌块的P-手性膦-噁唑啉配体金属络合物催化剂的制备及应用 - Google Patents
一种含Ugi’s胺砌块的P-手性膦-噁唑啉配体金属络合物催化剂的制备及应用 Download PDFInfo
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- 239000003446 ligand Substances 0.000 title claims abstract description 40
- NHFAABIHBNXKDT-UHFFFAOYSA-N 4,5-dihydro-1,3-oxazole;phosphane Chemical compound P.C1CN=CO1 NHFAABIHBNXKDT-UHFFFAOYSA-N 0.000 title claims abstract description 30
- 150000001412 amines Chemical class 0.000 title claims abstract description 30
- 239000003054 catalyst Substances 0.000 title claims abstract description 17
- 150000004696 coordination complex Chemical class 0.000 title claims abstract description 11
- 238000002360 preparation method Methods 0.000 title claims description 7
- 238000009876 asymmetric hydrogenation reaction Methods 0.000 claims abstract description 15
- 230000003197 catalytic effect Effects 0.000 claims abstract description 13
- 229910052751 metal Inorganic materials 0.000 claims abstract description 5
- 239000002184 metal Substances 0.000 claims abstract description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 claims description 27
- 229910052760 oxygen Inorganic materials 0.000 claims description 17
- 238000006243 chemical reaction Methods 0.000 claims description 15
- 125000000524 functional group Chemical group 0.000 claims description 14
- 229910052757 nitrogen Inorganic materials 0.000 claims description 14
- 229910052717 sulfur Inorganic materials 0.000 claims description 14
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 12
- 125000003118 aryl group Chemical group 0.000 claims description 12
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical group [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 10
- 125000001931 aliphatic group Chemical group 0.000 claims description 8
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- 238000006555 catalytic reaction Methods 0.000 claims description 6
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 6
- 238000005057 refrigeration Methods 0.000 claims description 5
- 239000002904 solvent Substances 0.000 claims description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 230000015572 biosynthetic process Effects 0.000 claims description 4
- 238000001035 drying Methods 0.000 claims description 4
- 229910052742 iron Inorganic materials 0.000 claims description 4
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 claims description 4
- 238000000034 method Methods 0.000 claims description 4
- 239000010948 rhodium Substances 0.000 claims description 4
- 238000003756 stirring Methods 0.000 claims description 4
- 238000003786 synthesis reaction Methods 0.000 claims description 4
- 238000004440 column chromatography Methods 0.000 claims description 3
- IMDXZWRLUZPMDH-UHFFFAOYSA-N dichlorophenylphosphine Chemical compound ClP(Cl)C1=CC=CC=C1 IMDXZWRLUZPMDH-UHFFFAOYSA-N 0.000 claims description 3
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 claims description 2
- CXBNMPMLFONTPO-UHFFFAOYSA-N acetic benzoic anhydride Chemical class CC(=O)OC(=O)C1=CC=CC=C1 CXBNMPMLFONTPO-UHFFFAOYSA-N 0.000 claims description 2
- 230000003213 activating effect Effects 0.000 claims description 2
- 239000012298 atmosphere Substances 0.000 claims description 2
- 150000001735 carboxylic acids Chemical class 0.000 claims description 2
- 239000007810 chemical reaction solvent Substances 0.000 claims description 2
- 238000006392 deoxygenation reaction Methods 0.000 claims description 2
- 238000001704 evaporation Methods 0.000 claims description 2
- GNNILMDCYQGMRH-UHFFFAOYSA-N formyl benzoate Chemical class O=COC(=O)C1=CC=CC=C1 GNNILMDCYQGMRH-UHFFFAOYSA-N 0.000 claims description 2
- 239000011261 inert gas Substances 0.000 claims description 2
- 229910052741 iridium Inorganic materials 0.000 claims description 2
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 claims description 2
- WGOPGODQLGJZGL-UHFFFAOYSA-N lithium;butane Chemical compound [Li+].CC[CH-]C WGOPGODQLGJZGL-UHFFFAOYSA-N 0.000 claims description 2
- 229910052763 palladium Inorganic materials 0.000 claims description 2
- ZFJMTDFOGDGPTF-UHFFFAOYSA-N phosphanium;chloride;hydrochloride Chemical compound P.Cl.Cl ZFJMTDFOGDGPTF-UHFFFAOYSA-N 0.000 claims description 2
- 229910052697 platinum Inorganic materials 0.000 claims description 2
- 239000002243 precursor Substances 0.000 claims description 2
- 238000010791 quenching Methods 0.000 claims description 2
- 230000000171 quenching effect Effects 0.000 claims description 2
- 239000000376 reactant Substances 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
- 239000011949 solid catalyst Substances 0.000 claims description 2
- 239000002994 raw material Substances 0.000 abstract description 9
- 238000006138 lithiation reaction Methods 0.000 abstract description 3
- 150000001336 alkenes Chemical class 0.000 abstract description 2
- KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical group [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 abstract description 2
- 150000002466 imines Chemical class 0.000 abstract description 2
- 150000002576 ketones Chemical class 0.000 abstract description 2
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 abstract description 2
- IMSODMZESSGVBE-UHFFFAOYSA-N 2-Oxazoline Chemical compound C1CN=CO1 IMSODMZESSGVBE-UHFFFAOYSA-N 0.000 abstract 1
- USJRLGNYCQWLPF-UHFFFAOYSA-N chlorophosphane Chemical compound ClP USJRLGNYCQWLPF-UHFFFAOYSA-N 0.000 abstract 1
- LWNLXVXSCCLRRZ-UHFFFAOYSA-N dichlorophosphane Chemical compound ClPCl LWNLXVXSCCLRRZ-UHFFFAOYSA-N 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 32
- 238000005160 1H NMR spectroscopy Methods 0.000 description 8
- 238000004679 31P NMR spectroscopy Methods 0.000 description 8
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- HVCLJUVMOVVZBS-NSHDSACASA-N (4r)-2-(2-bromophenyl)-4-propan-2-yl-4,5-dihydro-1,3-oxazole Chemical compound CC(C)[C@@H]1COC(C=2C(=CC=CC=2)Br)=N1 HVCLJUVMOVVZBS-NSHDSACASA-N 0.000 description 2
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
- 239000012300 argon atmosphere Substances 0.000 description 2
- 238000011914 asymmetric synthesis Methods 0.000 description 2
- VURFVHCLMJOLKN-UHFFFAOYSA-N diphosphane Chemical compound PP VURFVHCLMJOLKN-UHFFFAOYSA-N 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- NJQJYOLYDOCZGX-NSHDSACASA-N (4R)-2-(2-bromophenyl)-4-tert-butyl-4,5-dihydro-1,3-oxazole Chemical compound CC(C)(C)[C@@H]1COC(=N1)c1ccccc1Br NJQJYOLYDOCZGX-NSHDSACASA-N 0.000 description 1
- JCBMLLAMAYJGFH-ZDUSSCGKSA-N (4S)-4-benzyl-2-(2-bromophenyl)-4,5-dihydro-1,3-oxazole Chemical compound BrC1=CC=CC=C1C(OC1)=N[C@H]1CC1=CC=CC=C1 JCBMLLAMAYJGFH-ZDUSSCGKSA-N 0.000 description 1
- HVCLJUVMOVVZBS-LLVKDONJSA-N (4s)-2-(2-bromophenyl)-4-propan-2-yl-4,5-dihydro-1,3-oxazole Chemical compound CC(C)[C@H]1COC(C=2C(=CC=CC=2)Br)=N1 HVCLJUVMOVVZBS-LLVKDONJSA-N 0.000 description 1
- NJQJYOLYDOCZGX-LLVKDONJSA-N (4s)-2-(2-bromophenyl)-4-tert-butyl-4,5-dihydro-1,3-oxazole Chemical compound CC(C)(C)[C@H]1COC(C=2C(=CC=CC=2)Br)=N1 NJQJYOLYDOCZGX-LLVKDONJSA-N 0.000 description 1
- -1 (S) -2- (2-bromophenyl) -4-phenyl-4, 5-dihydrooxazole Chemical compound 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- JCBMLLAMAYJGFH-CYBMUJFWSA-N C1[C@H](N=C(O1)C2=CC=CC=C2Br)CC3=CC=CC=C3 Chemical compound C1[C@H](N=C(O1)C2=CC=CC=C2Br)CC3=CC=CC=C3 JCBMLLAMAYJGFH-CYBMUJFWSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 208000012839 conversion disease Diseases 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F17/00—Metallocenes
- C07F17/02—Metallocenes of metals of Groups 8, 9 or 10 of the Periodic Table
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/24—Phosphines, i.e. phosphorus bonded to only carbon atoms, or to both carbon and hydrogen atoms, including e.g. sp2-hybridised phosphorus compounds such as phosphabenzene, phosphole or anionic phospholide ligands
- B01J31/2404—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring
- B01J31/2409—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring with more than one complexing phosphine-P atom
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/347—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups
- C07C51/36—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by hydrogenation of carbon-to-carbon unsaturated bonds
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
- B01J2231/60—Reduction reactions, e.g. hydrogenation
- B01J2231/64—Reductions in general of organic substrates, e.g. hydride reductions or hydrogenations
- B01J2231/641—Hydrogenation of organic substrates, i.e. H2 or H-transfer hydrogenations, e.g. Fischer-Tropsch processes
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Abstract
一种含Ugi’s胺砌块的P‑手性膦‑噁唑啉配体金属络合物催化剂的制备及应用，配体是以手性Ugi’s胺为原料，邻位锂化后与二氯膦代物反应得到单氯膦代物，继续与邻位锂化的恶唑啉反应，得到具有P‑手性、中心手性和面手性的二茂铁骨架膦‑噁唑啉配体。本发明的P‑手性膦‑噁唑啉配体结构新颖、对空气稳定且合成简便，与金属形成的络合物催化剂在前手性烯烃、酮和亚胺等的不对称氢化反应中都表现出很高的催化活性和立体选择性。
Description
技术领域
本发明涉及一种催化剂，具体涉及一种含Ugi’s胺砌块的P-手性膦-噁唑啉配体金属络合物催化剂的制备及应用。
背景技术
目前获得手性化合物的方法主要有：外消旋体拆分、手性源合成和催化不对称合成，其中催化不对称合成是制备手性化合物最原子经济且绿色环保的方法。催化氢化反应是不对称催化反应中最为重要的反应之一，主要包括含C＝C、C＝O及C＝N双键前手性化合物的不对称氢化。目前虽然已经报道了很多优秀的手性配体用于不对称氢化反应，但由于催化活性不够好、对映选择性低和制备繁琐等原因走向实际应用的配体屈指可数。
膦-噁唑啉类配体是一类非常优秀手性配体，在许多不对称催化反应中都表现出优秀的催化活性和立体选择性。目前针对这类配体的改造多集中于取代基修饰，而对于手性因素的改造则很少见。P-手性因更接近金属中心往往具有较好的手性诱导，所以在双膦配体的发展过程中备受重视。二茂铁骨架具有高度热稳定性、化学稳定性和特殊的电子效应，在催化剂领域得到了广泛应用，发展一类同时具有面手性、中心手性、膦手性的P-手性膦-噁唑啉配体具有巨大应用价值。
发明内容
本发明的目的是提供一种含Ugi’s胺砌块的P-手性膦-噁唑啉配体金属络合物催化剂的制备及应用。
为了实现上述目的，本发明的具体方案是：
一种含Ugi’s胺砌块的P-手性膦-噁唑啉配体，其特征在于，分子结构式如式1所示：
式中：R1为烷基和环烷基的C1～C40内的含或不含N、S、O、P一种或多种官能团的脂肪基团；苄基的C7～C60在内的含或不含N、S、O、P一种或多种官能团的芳香基团与脂肪基团的组合基团；芳基的C6～C60内的含或不含N、S、O、P一种或多种官能团的芳香基团；
R2为芳基的C6～C60内的含或不含N、S、O、P一种或多种官能团的芳香基团；
R3为烷基和环烷基的C1～C40内的含或不含N、S、O、P一种或多种官能团的脂肪基团；苄基的C7～C60在内的含或不含N、S、O、P一种或多种官能团的芳香基团与脂肪基团的组合基团；芳基的C6～C60内的含或不含N、S、O、P一种或多种官能团的芳香基团。
一种含Ugi’s胺砌块的P-手性膦-噁唑啉配体的合成路线如下所示：
一种含Ugi’s胺砌块的P-手性膦-噁唑啉配体的配体合成步骤如下：
a)按摩尔比邻溴恶唑啉1：丁基锂＝1：1～1.5，在惰性气体氛围和低温(-40～-80℃)条件下，将丁基锂加入邻溴恶唑啉1的四氢呋喃溶液，滴毕后关闭制冷，反应2～3h，制得中间体2备用；
b)在冰浴下将丁基锂加入二茂铁胺3的醚溶液中，反应物与丁基锂的摩尔比为1：1～1.2，加毕后室温搅拌下反应1～6h，将反应液再置于低温(-40～-80℃)环境中，缓慢加入苯基二氯化膦，二氯化膦与二茂铁胺3的摩尔比为1～1.2：1，滴毕后关闭制冷，反应3～6h，制得中间体4；
c)将中间体4置于低温(-40～-80℃)环境中，将制好的中间体2通过双针头加入，关闭制冷，反应6～18h，淬灭，萃取后干燥，蒸干溶剂，柱层析得P-手性膦-噁唑啉配体A。
所述的活化邻溴恶唑啉1和二茂铁胺3的丁基锂选自正丁基锂、仲丁基锂或叔丁基锂的一种。
所述的锂化邻溴恶唑啉1和二茂铁胺3的反应溶剂选自乙醚、甲基叔丁基醚、四氢呋喃或甲苯的一种或两种以上。
所述的锂化邻溴恶唑啉1和二茂铁胺3的反应温度选自-40～-80℃；中间体2与中间体4反应温度选自-40～-80℃。
一种含Ugi’s胺砌块的P-手性膦-噁唑啉配体的金属络合物催化剂的制备方法，包括以下步骤：
按摩尔比配体：金属前体＝1.05～2.1：1，在脱氧溶剂中室温搅拌5～60min得到催化剂。
所述的金属前体是铁(Fe)、铁(Co)、铁(Ni)、钌(Ru)、铑(Rh)、铱(Ir)、钯(Pd)或铂(Pt)。
一种含Ugi’s胺砌块的P-手性膦-噁唑啉配体的金属络合物催化剂应用于不对称催化反应；或将溶液旋干得固体催化剂再进行后续催化反应。
一种含Ugi’s胺砌块的P-手性膦-噁唑啉配体的金属络合物催化剂在C＝C、C＝O、C＝N键中的不对称氢化反应中的应用：
1)不饱和羧酸类的不对称氢化反应；
2)苯或取代苯甲酰基乙酸酯类的催化不对称氢化反应；
3)苯或取代苯甲酰基甲酸酯类的催化不对称氢化反应；
3)N-烷基和N-芳基亚胺的催化不对称氢化。
本发明的有益效果是：
本发明的P-手性膦-噁唑啉配体结构新颖、对空气稳定且合成简便，与金属形成的络合物催化剂在前手性烯烃、酮和亚胺等的不对称氢化反应中都表现出很高的催化活性和立体选择性。
具体实施方式
本发明的技术特征已在发明内容部分作了较充分的说明，下面的实施实例是用来对本发明作进一步的描述，但不是对本发明的限定。
A、配体的合成
实施例1
向100mL Schlenk瓶中加入(R)-Ugi′s胺(5mmol,1.29g)，然后在氩气氛围下加入甲基叔丁基醚(8mL)，待Ugi′s胺完全溶解后缓慢将叔丁基锂(t-BuLi，1.3M inhexane,4.2mL)用注射器缓慢滴加进反应体系中，室温下反应2～3小时。紧接着将反应置于-78℃预冷5～10min，在-78℃下将苯基二氯化膦(5.5mmol,0.75mL)缓慢滴加入反应体系中，关掉低温反应器制冷，反应4～5小时，得中间体4。将反应原料(S)-2-(2-溴苯基)-4-异丙基-4,5-二氢噁唑(6.9mmol,1.85g)置于100mLSchlenk瓶中，氩气氛围下加入四氢呋喃(7.5mL)，在-78℃下缓慢滴加的正丁基锂(n-BuLi，1.6M in hexane,4.7mL)，滴加结束后关闭低温反应器制冷，反应2～3小时，得中间体2。将中间体2用注射器打入中间体4中，反应过夜。用饱和氯化铵水溶液(30mL)淬灭反应，用的乙酸乙酯萃取(3×50mL)，有机相用无水硫酸钠干燥，蒸干溶剂。柱层析法纯化(乙酸乙酯：石油醚：三乙胺＝10：4：1‰)，得(RC,SFc,SP,SC)-A11.85g，产率67％。1H NMR(400Hz,CDCl3)δ7.76–7.71(m,1H),7.57–7.49(m,2H),7.36–7.31(m,3H),7.23–7.17(m,2H),7.11–7.04(m,1H),4.38(s,1H),4.22(s,1H),4.16(dd,J＝6.7,3.0Hz,1H),4.10–4.03(m,1H),4.01–3.96(m,1H),3.95(s,5H),3.91–3.82(m,1H),3.68(s,1H),1.77(s,6H),1.70(dt,J＝13.3,6.7Hz,1H),1.23(d,J＝6.7Hz,3H),0.84(d,J＝6.7Hz,3H),0.67(d,J＝6.7Hz,3H)；31P NMR(162Hz,CDCl3)δ-22.92.
实施例2
以1.29g(R)-Ugi′s胺和1.85g(R)-2-(2-溴苯基)-4-异丙基-4,5-二氢噁唑为原料按相同步骤得(RC,SFc,SP,RC)-A11.60g，产率58％。1H NMR(400Hz,CDCl3)δ7.73–7.67(m,1H),7.57–7.50(m,2H),7.35–7.29(m,3H),7.22–7.16(m,2H),7.09–7.02(m,1H),4.38(s,1H),4.26–4.19(m,2H),4.15(dd,J＝6.9,3.0Hz,1H),3.93(s,5H),3.89–3.84(m,1H),3.79(t,J＝8.0Hz,1H),3.70(s,1H),1.77(s,6H),1.59(dd,J＝13.4,6.7Hz,2H),1.23(d,J＝6.7Hz,3H),0.94(d,J＝6.7Hz,3H),0.80(d,J＝6.8Hz,3H)；31P NMR(162Hz,CDCl3)δ-23.80.
实施例3
以1.22g(R)-Ugi′s胺和2.0g(S)-2-(2-溴苯基)-4-叔丁基-4,5-二氢噁唑为原料按相同步骤得(RC,SFc,SP,SC)-A22.10g，产率78％。1H NMR(400Hz,CDCl3)δ7.78–7.72(m,1H),7.54–7.48(m,2H),7.34–7.29(m,3H),7.22–7.17(m,2H),7.05–6.99(m,1H),4.38(s,1H),4.22(s,1H),4.15(dd,J＝6.8,3.0Hz,1H),4.13–4.07(m,1H),3.98(s,1H),3.95(s,5H),3.75–3.68(m,1H),3.65(s,1H),1.80(s,6H),1.24(d,J＝6.7Hz,3H),0.78(s,9H)；31PNMR(162Hz,CDCl3)δ-22.35.
实施例4
以1.22g(R)-Ugi′s胺和2.0g(R)-2-(2-溴苯基)-4-叔丁基-4,5-二氢噁唑为原料按相同步骤得(RC,SFc,SP,RC)-A21.90g，产率70％。1H NMR(400Hz,CDCl3)δ7.79–7.71(m,1H),7.55–7.49(m,2H),7.36–7.28(m,3H),7.23–7.17(m,2H),7.12–7.04(m,1H),4.36(s,1H),4.25–4.16(m,2H),4.14–4.10(m,1H),3.95(s,5H),3.92–3.84(m,2H),3.65(s,1H),1.70(s,6H),1.20(d,J＝7.4Hz,3H),0.90(s,9H)；31P NMR(162Hz,CDCl3)δ-25.40.
实施例5
以1.22g(R)-Ugi′s胺和2.0g(S)-2-(2-溴苯基)-4-苯基-4,5-二氢噁唑为原料按相同步骤得(RC,SFc,SP,SC)-A30.80g，产率30％。1HNMR(400Hz,CDCl3)δ7.90–7.80(m,1H),7.53–7.47(m,2H),7.36–7.28(m,4H),7.28–7.17(m,4H),7.14–7.07(m,1H),7.05–6.95(m,2H),5.26–5.18(m,1H),4.53–4.46(m,1H),4.39(s,1H),4.23(s,1H),4.19(dd,J＝6.8,3.0Hz,1H),4.11(t,J＝8.3Hz,1H),3.95(s,5H),3.68(s,1H),1.77(s,6H),1.23(d,J＝7.1Hz,3H)；31P NMR(162Hz,CDCl3)δ-22.94.
实施例6
以1.26g(R)-Ugi′s胺和2.2g(R)-2-(2-溴苯基)-4-异丙基-4,5-二氢噁唑为原料按相同步骤得(RC,SFc,SP,RC)-A30.90g，产率35％。1H NMR(400Hz,CDCl3)δ7.85–7.78(m,1H),7.58–7.51(m,2H),7.38–7.33(m,3H),7.27–7.17(m,5H),7.09–7.04(m,1H),7.00–6.92(m,2H),5.15(t,J＝9.6Hz,1H),4.76–4.59(m,1H),4.41(s,1H),4.24(s,1H),4.21(dd,J＝6.6,2.9Hz,1H),3.92(s,5H),3.92–3.82(m,1H),3.72(s,1H),1.84(s,6H),1.25(d,J＝6.9Hz,3H)；31P NMR(162Hz,CDCl3)δ-22.38.
实施例7
以1.26g(R)-Ugi′s胺和2.2g(S)-2-(2-溴苯基)-4-苄基-4,5-二氢噁唑为原料按相同步骤得(RC,SFc,SP,SC)-A41.50g，产率51％。1HNMR(400Hz,CDCl3)δ7.77–7.70(m,1H),7.59–7.51(m,2H),7.33–7.30(m,3H),7.27–7.16(m,5H),7.10–7.02(m,3H),4.45–4.32(m,2H),4.28–4.18(m,2H),4.02–3.96(m,1H),3.96(s,5H),3.94–3.89(m,1H),3.68(s,1H),3.04(dd,J＝13.8,4.7Hz,1H),2.27(dd,J＝13.8,9.4Hz,1H),1.82(s,6H),1.26(s,3H)；31PNMR(162Hz,CDCl3)δ-22.23.
实施例8
以1.26g(R)-Ugi′s胺和2.2g(R)-2-(2-溴苯基)-4-苄基-4,5-二氢噁唑为原料按相同步骤得(RC,SFc,SP,RC)-A41.65g，产率57％。1HNMR(400Hz,CDCl3)δ7.70–7.63(m,1H),7.58–7.50(m,2H),7.41–7.35(m,3H),7.34–7.29(m,2H),7.25–7.12(m,5H),7.05–6.99(m,1H),4.41(s,1H),4.34–4.27(m,1H),4.24(s,1H),4.21–4.17(m,1H),4.13–4.07(m,1H),3.91(s,5H),3.77–3.73(m,1H),3.72(s,1H),2.98(dd,J＝13.7,5.0Hz,1H),2.07(dd,J＝13.7,9.5Hz,1H),1.87(s,6H),1.26(s,3H)；31P NMR(162Hz,CDCl3)δ-22.00.
B、催化不对称氢化反应
实施实例9
在氮气保护下，[Ir(COD)Cl]2(1.7mg,0.0025mmol)和P-手性膦-噁唑啉配体(RC,SFc,SP,SC)-A2(3.1mg,0.0055mmol)和1mL甲醇置于Schlenk反应管中，搅拌反应30min，加反应底物5(75mg,0.5mmol)的甲醇溶液，然后转移到氢化釜中在50℃和50atm H2下反应18h，用短硅胶柱过滤，将过滤所得滤液浓缩后得产物(R)-6，GC测反应转化率97％，对映体过量51％ee。
Claims (10)
1.一种含Ugi’s胺砌块的P-手性膦-噁唑啉配体，其特征在于，分子结构式如式1所示：
式中：R1为烷基和环烷基的C1～C40内的含或不含N、S、O、P一种或多种官能团的脂肪基团；苄基的C7～C60在内的含或不含N、S、O、P一种或多种官能团的芳香基团与脂肪基团的组合基团；芳基的C6～C60内的含或不含N、S、O、P一种或多种官能团的芳香基团；
R2为芳基的C6～C60内的含或不含N、S、O、P一种或多种官能团的芳香基团；
R3为烷基和环烷基的C1～C40内的含或不含N、S、O、P一种或多种官能团的脂肪基团；苄基的C7～C60在内的含或不含N、S、O、P一种或多种官能团的芳香基团与脂肪基团的组合基团；芳基的C6～C60内的含或不含N、S、O、P一种或多种官能团的芳香基团。
2.根据权利要求1所述的一种含Ugi’s胺砌块的P-手性膦-噁唑啉配体，其特征在于，合成路线如下所示：
3.根据权利要求1所述的一种含Ugi’s胺砌块的P-手性膦-噁唑啉配体，其特征在于，配体合成步骤如下：
a)按摩尔比邻溴恶唑啉1：丁基锂＝1：1～1.5，在惰性气体氛围和低温(-40～-80℃)条件下，将丁基锂加入邻溴恶唑啉1的四氢呋喃溶液，滴毕后关闭制冷，反应2～3h，制得中间体2备用；
b)在冰浴下将丁基锂加入二茂铁胺3的醚溶液中，反应物与丁基锂的摩尔比为1：1～1.2，加毕后室温搅拌下反应1～6h，将反应液再置于低温(-40～-80℃)环境中，缓慢加入苯基二氯化膦，二氯化膦与二茂铁胺3的摩尔比为1～1.2：1，滴毕后关闭制冷，反应3～6h，制得中间体4；
c)将中间体4置于低温(-40～-80℃)环境中，将制好的中间体2通过双针头加入，关闭制冷，反应6～18h，淬灭，萃取后干燥，蒸干溶剂，柱层析得P-手性膦-噁唑啉配体A。
4.根据权利要求3所述的一种含Ugi’s胺砌块的P-手性膦-噁唑啉配体，其特征在于，所述的活化邻溴恶唑啉1和二茂铁胺3的丁基锂选自正丁基锂、仲丁基锂或叔丁基锂的一种。
5.根据权利要求3所述的一种含Ugi’s胺砌块的P-手性膦-噁唑啉配体，其特征在于，所述的锂化邻溴恶唑啉1和二茂铁胺3的反应溶剂选自乙醚、甲基叔丁基醚、四氢呋喃或甲苯的一种或两种以上。
6.根据权利要求3所述的一种含Ugi’s胺砌块的P-手性膦-噁唑啉配体，其特征在于，所述的锂化邻溴恶唑啉1和二茂铁胺3的反应温度选自-40～-80℃；中间体2与中间体4反应温度选自-40～-80℃。
7.一种含Ugi’s胺砌块的P-手性膦-噁唑啉配体的金属络合物催化剂的制备方法，其特征在于，包括以下步骤：
按摩尔比配体：金属前体＝1.05～2.1：1，在脱氧溶剂中室温搅拌5～60min得到催化剂。
8.根据权利要求7所述的一种含Ugi’s胺砌块的P-手性膦-噁唑啉配体的金属络合物催化剂的制备方法，其特征在于，所述的金属前体是铁(Fe)、铁(Co)、铁(Ni)、钌(Ru)、铑(Rh)、铱(Ir)、钯(Pd)或铂(Pt)。
9.一种含Ugi’s胺砌块的P-手性膦-噁唑啉配体的金属络合物催化剂应用于不对称催化反应；或将溶液旋干得固体催化剂再进行后续催化反应。
10.一种含Ugi’s胺砌块的P-手性膦-噁唑啉配体的金属络合物催化剂在C＝C、C＝O、C＝N键中的不对称氢化反应中的应用：
1)不饱和羧酸类的不对称氢化反应；
2)苯或取代苯甲酰基乙酸酯类的催化不对称氢化反应；
3)苯或取代苯甲酰基甲酸酯类的催化不对称氢化反应；
3)N-烷基和N-芳基亚胺的催化不对称氢化。
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