CN105879905A - Polyfunctional chiral phosphine catalyst and its preparation method and use - Google Patents
Polyfunctional chiral phosphine catalyst and its preparation method and use Download PDFInfo
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Abstract
The invention relates to a polyfunctional chiral phosphine catalyst, a preparation method of the polyfunctional chiral phosphine catalyst and a use of the polyfunctional chiral phosphorus catalyst in an asymmetric intermolecular cross Rauhut-Currier (RC) reaction. The compound contains two Bronsted acid parts of amide and phenolic hydroxyl groups and a Lewis base part of trivalent phosphine, effectively catalyzes an asymmetric intermolecular cross RC reaction and realizes production of a corresponding single cross RC reaction product with a good yield and good enantioselectivity. The preparation method is the first chiral phosphine catalytic asymmetric intermolecular cross RC reaction and has the highest ee value of 90%. The polyfunctional chiral phosphine catalyst has a structure shown in the description.
Description
Technical field
The present invention relates to a kind of polyfunctional group chiral phosphine compound, preparation method and the application in Rauhut-Currier reaction (RC reaction) that intersects between asymmetric molecult thereof.This compounds contains amide groups and phenolic hydroxyl group twoThe part of acid and the part of the Lewis alkali of a trivalent phosphine, it is possible to obtain the product of the most single intersection RC reaction with good yield and enantioselectivity.It it is the asymmetric version of the intermolecular intersection RC reaction of the first chiral phosphine catalysis of report at present.
Background technology
Rauhut-Currier reaction be 1963 by Rauhut and Currier report use tertiary phosphine catalysis construct carbon-carbon bond reaction (M.M.Rauhut, H.Currier, U.S.Patent, 1963,3074999；Chem.Abstr., 1963,58,11224a.).Due to the activity difference between different activated olefins so that course of reaction exists intersection RC reaction and the competition of molecule dimerization reaction, is at best able to obtain four kinds of different products.Owing to lacking, this reactive chemistry is the most effectively controlled so that this reaction application in organic synthesis by the biggest limited.2002, Roush and Krische achieves intramolecular RC reaction, be there is the group of large space steric hindrance by the electrical of two kinds of different alkene of regulation or introducing, reaction is made to be provided with good chemo-selective (S.A.Frank, D.J.Mergott, W.R.Roush, J.Am.Chem.Soc.2002,124,2404-2405；L.Wang, A.L.Lius, K.Agapiou, H.Y.Jang, M.J.Krische, J.Am.Chem.Soc.2002,124,2402-2403.).DBU afterwards, azepine Cabbeen, imidazoles/LiCl substitutes tertiary phosphine intersection RC between catalytic molecular used also as catalyst and reacts (J.R.Hwu, G.H.Hakimelahi, C.T.Chou, Tetra.Lett.1992,33,6469-6472；R.L.Atienza, K.A.Scheidt, Aust.J.Chem.2011,64,1158-1164；P.Shanbhag, P.R.Nareddy, M.Dadwal, S.M.Mobin, I.N.N.Namboothiri, Org.Biomol.Chem.2010,8,4867-4873；R.Kumar, T.Kumar, S.M.Mobin, I.N.N.Nambothiri, J.Org.Chem.2013,78,5073-5077；R.Zhou, J.Wang, J.Yu, Z.He, J.Org.Chem.2013,78,10596-10604.).Asymmetric research about RC reaction is confined to intramolecular mostly, the catalyst used has Cys (C.E.Aroyan, S.J.Miller, J.Am.Chem.Soc.2007,129,256-257.), diphenylprolinol silicon ether (E.Marqu é s-L ó pez, R.P.Herrera, T.Marks, W.C.Jacobs, D.R.M.de Figueiredo, M.Christmann, Org.Lett.2009,11,4116-4119.), chiral phosphine reagent (S.Takizawa, T.M.N.Nguyen, A.Grossmann, D.Enders, H.Sasai, Angew.Chem.2012,124,5519-5522；Angew.Chem.Int.Ed.2012,51,5423-5426；I) S.Takizawa, T.M.N.Nguyen, A.Grossmann, D.Enders, H.Sasai, Tetrahedron 2013,69,1202-1209.) and the little molecule organic catalyst (X.Zhang of other hydrogen bonds, M.Shi, Eur.J.Org.Chem.2012,6271-6279.).The connection olefin(e) acid ester using beta-schardinger dextrin catalysis of quick report is the most only executed for the research of intermolecular intersection RC reaction and the RC that intersects of maleimide reacts (Q.Zhao, C.Pei, X.Guan, M.Shi, Adv.Synth.Catal.2011,353,1973-1979.).And the intermolecular asymmetric research of the RC being catalyzed by the tertiary phosphine reaction for being originally found there is no report so far.
The research of the asymmetric reaction of difunctional organic catalyst catalysis in recent years gets more and more, and among these catalyst, amido (mainly with acid amides, thiocarbamide, side amine, urea, the form of dipeptides) and phenolic hydroxyl group are mainThe part of acid, optionally can control with the form realization of hydrogen bond in course of reaction (P.Chauhan, S.S.Chimni, Rsc Advances2012,2,737-758；A.Ting, J.M.Goss, N.T.McDougal, S.E.Schaus, Top.Curr.Chem.2009,291,201-232；X.Liu, L.Lin, X.Feng, Chem.Commun.2009,6145-6158.).But the research of polyfunctional group catalyst is the most few.Liu thinks that polyfunctional group catalyst can improve the speed (J.M.Gamier of the catalytic efficiency of catalyst, the selectivity of reaction and reaction in the way of polyfunctional group activation, C.Anstiss, F.Liu, Adv.Synth.Catal.2009,351,331-338).We using amide groups and phenolic hydroxyl group asThe part of acid, will be used for the trivalent phosphine the being catalyzed RC reaction part as Lewis alkali, has synthesized a kind of novel polyfunctional group chiral phosphine catalyst with natural amino acid for frame design, and this catalyst is successfully applied to intermolecular intersection RC reaction.
Summary of the invention
It is an object of the invention to provide a kind of polyfunctional group chiral phosphine compound.
The purpose of the present invention also provides for the preparation method of a kind of above-mentioned polyfunctional group chiral phosphine compound.
It is a further object to provide the application in the intermolecular intersection RC of asymmetry catalysis reacts of a kind of above-mentioned polyfunctional group chiral phosphine compound.
The polyfunctional group chiral phosphine compound related in the present invention has a chemical combination structural formula as follows:
Wherein R is alkyl, benzyl.R1For methyl, C1-C4 alkoxyl, halogen, nitro.
The polyfunctional group phosphine compound of the present invention can be obtained by condensation reaction with substituted salicylic acid or 3-hydroxyl 2-naphthoic acid by known compound.
The most in organic solvent under the conditions of 0 DEG C, substituted amido phosphine compound and adjacent hydroxyaryl formic acid are with 1: the mol ratio of 1-1: 1.5 reacts 6-24h under conditions of condensing agent and organic base exist, and generates polyfunctional group chiral phosphine catalyst.The preferred DMF of organic solvent, oxolane, Isosorbide-5-Nitrae-dioxane one or more；The preferred BOP of condensing agent (BTA-1-base epoxide three (dimethylamino) phosphorus hexafluorophosphate), DCC (dicyclohexylcarbodiimide)/DMAP (DMAP), CDI (N, N '-carbonyl dimidazoles)；The preferred pyridine of organic base, triethylamine.
The polyfunctional group chiral phosphine compound of the present invention, can be used for asymmetry catalysis intermolecular intersection RC reaction, and concrete reaction equation is as follows:
Embodiment
Below it is implemented with and helps understand the present invention, but be not limited to present disclosure.
Embodiment 1:(S)-N-(1-(diphenylphosphine)-3-methybutane-2-)-2-Hydroxylbenzamide
100mg (0.37mmol) (S)-1-(diphenylphosphine)-3-methybutane-2-amine is dissolved in the THF that 3mL is dried, 58.5mg (0.42mmol) salicylic acid is added in 0 DEG C, 207mg (0.47mmol) BOP, 224mg (2.214mmol) triethylamine, 12h is reacted at 0 DEG C, by TLC monitoring reaction, after question response terminates, system adds saturated sodium bicarbonate aqueous solution and ethyl acetate extraction, merge organic phase, it is dried with anhydrous sodium sulfate, filter, filtrate rotation steaming obtains residue, use silica gel column chromatography to purify and obtain 94mg, productivity is 65%.
Product structure data characterization is as follows: fusing point: 98-100 DEG C；[α]29D=+13.7 (c 1.0, CH2Cl2)；1H NMR (400MHz, CDCl3) δ 12.33 (s, 1H), 7.52-7.26 (m, 11H), 6.93 (dt, J=9.7,4.9Hz, 1H), 6.82 (dt, J=8.0,3.9Hz, 1H), 6.72-6.65 (m, 1H), 6.01 (d, J=9.0Hz, 1H), 4.29-4.09 (m, 1H), 2.46-2.29 (m, 2H), 2.07 (dp, J=13.3,6.7Hz, 1H), 0.96 (d, J=1.5Hz, 3H), 0.94 (d, J=1.5Hz, 3H)；13C NMR (101MHz, CDCl3) δ 169.29 (s), 161.51 (s), 138.13 (t, J=11.9Hz), 134.01 (s), 132.83 (dd, J=19.3,9.3Hz), 129.08-128.55 (m), 125.16 (s), 118.42 (d, J=2.9Hz), 114.26 (s), 52.84 (d, J=13.6Hz), 32.77 (d, J=8.2Hz), 31.32 (d, J=15.0Hz), (s), 18.87 18.25 (s)；31P NMR (162MHz, CDCl3)δ-23.59(s)；HRMS(ESI)C24H26NO2P[M+H]+: calculated value: 392.1774: measured value: 392.1767.
Embodiment 2:(S)-N-(1-(diphenylphosphine)-3-phenyl-propane-2-)-2-Hydroxylbenzamide
Synthetic method, with embodiment 1, uses (S)-1-(diphenylphosphine)-3-phenyl-propane-2-amine as raw material, yield 65%.
Product structure data characterization is as follows: fusing point: 160-163 DEG C；[α]29 D=+13.5 (c 1.0, CH2Cl2)；1H NMR (400MHz, CDCl3) δ 12.27 (s, 1H), 7.55-7.14 (m, 16H), 6.93 (d, J=8.3Hz, 1H), 6.79-6.60 (m, 1H), 6.10 (d, J=7.7Hz, 1H), 4.61-4.40 (m, 1H), (3.13 dd, J=13.6,5.3Hz, 1H), (3.04 dd, J=13.5,7.1Hz, 1H), 2.39 (qd, J=14.2,6.8Hz, 1H).13C NMR (101MHz, CDCl3) δ 169.23 (s), 161.56 (s), 137.75 (dd, J=12.1,8.1Hz), 137.27 (s), 134.10 (s), 132.82 (dd, J=19.3,9.1Hz), 129.61 (s), 129.29-128.57 (m), 126.84 (s), 125.19 (s), 118.46 (s), 114.14 (s), 49.18 (d, J=14.7Hz), 41.22 (d, J=8.6Hz), 32.62 (d, J=15.4Hz).31P NMR (162MHz, CDCl3)δ-24.37(s)；HRMS(ESI)C28H26NO2P[M+H]+: calculated value: 440.1774；Measured value: 440.1781.
Embodiment 3:(S)-N-(1-(diphenylphosphine)-3-methylpentane-2-)-2-Hydroxylbenzamide
Synthetic method, with embodiment 1, uses (S)-1-(diphenylphosphine)-3-methylpentane-2-amine as raw material, yield 67%.
Product structure data characterization is as follows: fusing point: 73-74 DEG C；[α]29 D=+8.8 (c 1.0, CH2Cl2)；1H NMR (400MHz, CDCl3) δ 12.32 (s, 1H), 7.37 (dt, J=36.5, 12.5Hz, 11H), 6.94 (d, J=8.2Hz, 1H), 6.78 (d, J=7.4Hz, 1H), 6.69 (t, J=7.4Hz, 1H), 6.00 (d, J=7.7Hz, 1H), 4.28 (s, 1H), 2.41 (d, J=12.0Hz, 1H), 2.37-2.29 (m, 1H), 1.84 (m, 1H), 1.48 (d, J=6.2Hz, 1H), 1.15 (dt, J=21.6, 7.6Hz, 1H), 0.94 (d, J=6.5Hz, 3H), 0.88 (t, J=7.1Hz, 3H)；13C NMR (101MHz, CDCl3) δ 169.14 (s), 161.52 (s), 138.12 (dd, J=31.7, 12.7Hz), 138.12 (dd, J=31.7, 12.7Hz), 133.98 (s), 132.82 (t, J=18.8Hz), 129.25-128.49 (m), 125.13 (s), 118.40 (d, J=6.4Hz), 114.25 (s), 51.80 (d, J=13.5Hz), 39.12 (d, J=7.7Hz), 30.33 (d, J=14.7Hz), 25.48 (s), 14.90 (s), 11.63 (s)；31P NMR (162MHz, CDCl3)δ-23.40(s)；HRMS(ESI)m/z C25H28NO2P[M+H]+: calculated value: 406.1930；Measured value: 406-1937.
Embodiment 4:(S)-N-(1-(diphenylphosphine)-3-methylpentane-2-)-3-hydroxyl 2-naphthalenecarboxamide
Synthetic method, with embodiment 1, uses 3-hydroxy-2-naphthoic acid and (S)-1-(diphenylphosphine)-3-methylpentane-2-amine as raw material, yield 64%.
Product structure data characterization is as follows: fusing point: 118-120 DEG C；[α]29 D=+141.3 (c 1.0, CH2Cl2)；1H NMR (400MHz, CDCl3) δ 11.82 (s, 1H), 7.62 (dd, J=17.6,8.2Hz, 2H), 7.45 (dt, J=20.6,6.6Hz, 6H), 7.37-7.20 (m, 10H), 6.20 (d, J=8.6Hz, 1H), 4.47-4.26 (m, 1H), 2.42 (q, J=14.2Hz, 2H), 1.88 (m, 1H), 1.61-1.46 (m, 1H), 1.19 (dd, J=13.4,7.6Hz, 1H), 0.98 (d, J=6.6Hz, 4H), 0.90 (t, J=7.2Hz, 4H)；13C NMR (101MHz, CDCl3) δ 168.96 (s), 156.77 (s), 138.39 (s), 138.07 (s), 136.97 (s), 132.85 (dd, J=19.4,3.5Hz), 129.29-128.51 (m), 128.35 (s), 126.97-126.07 (m), 123.68 (s), 116.91 (s), 112.17 (s), 52.25 (d, J=13.8Hz), 39.28 (d, J=7.9Hz), 30.24 (d, J=14.5Hz), 29.75 (s), 25.62 (s), 14.96 (s), 11.65 (s)；31P NMR (162MHz, CDCl3)δ-23.15(s)；HRMS(ESI)m/zC29H30NO2P[M+H]+: calculated value: 456.2087；Measured value: 456.2094.
Embodiment 5: the asymmetric research of the intermolecular intersection RC reaction of polyfunctional group chiral phosphine catalyst
By 0.1mmol substrate; 10mol% polyfunctional group chiral phosphine catalyst is dissolved in 0.5mL chloroform; add 0.3mmol methyl vinyl ketone; 16 DEG C of reactions under conditions of argon shield; TLC monitors reaction; after question response terminates, directly carry out column chromatography for separation, use petrol ether/ethyl acetate=10: 1 as eluant, eluent.Ee value chirality HPLC measures, and the results are shown in Table 1.
Table 1: the asymmetric research of the intermolecular intersection RC reaction of catalyst involved in the present invention
Claims (4)
1. a polyfunctional group chiral phosphine catalyst, is characterized in that having following structural formula:
Wherein R is alkyl, benzyl.R1For methyl, C1-C4 alkoxyl, halogen, nitro.
2. the preparation method of polyfunctional group chiral phosphine catalyst as claimed in claim 1, is characterized in that 0 DEG C in organic solvent
Under the conditions of, substituted amino phosphine compound and adjacent hydroxyaryl formic acid are with 1: the mol ratio of 1-1: 1.5 is deposited at condensing agent and organic base
React 6-24h under the conditions, generate polyfunctional group chiral phosphine catalyst.The preferred DMF of organic solvent, four
Hydrogen furans, Isosorbide-5-Nitrae-dioxane one or more；The preferred BOP of condensing agent (BTA-1-base epoxide three (dimethylamino
Base) phosphorus hexafluorophosphate), DCC (dicyclohexylcarbodiimide)/DMAP (DMAP), CDI (N, N '-
Carbonyl dimidazoles)；The preferred pyridine of organic base, triethylamine.
3. the application of polyfunctional group chiral phosphine compound as claimed in claim 1, is characterized in that this compound is for asymmetric point
The Rauhut-Currier that intersects between son reacts the chiral organic micromolecule catalyst of (RC reaction).
4. the application of the polyfunctional group chiral phosphine compound as described in right 3, it is characterized in that described asymmetric catalysis for
Prepare the chipal compounds of following structural formula:
Wherein: Ar is aryl, the substituted-phenyl such as including phenyl, halogen, alkyl, alkoxyl, the heteroaryl such as furyl, thienyl
Base.Wherein aryl includes the heteroaryls such as the substituted phenyl such as phenyl, halogen, alkyl, alkoxyl, furans, thiophene.R1For alkane
Base, including methyl, ethyl, isopropyl, benzyl etc..
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| CN111790439A (en) * | 2020-07-29 | 2020-10-20 | 南宁师范大学 | Chiral secondary amine diphenylphosphine arylformamide bifunctional catalyst and preparation method and application thereof |
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| JP5313335B2 (en) * | 2008-04-25 | 2013-10-09 | 浙江九洲▲薬▼▲業▼股▲分▼有限公司 | Application of iridium complexes in the catalytic asymmetric hydrogenation of unsaturated carboxylic acids |
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| CN111790439A (en) * | 2020-07-29 | 2020-10-20 | 南宁师范大学 | Chiral secondary amine diphenylphosphine arylformamide bifunctional catalyst and preparation method and application thereof |
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