CN1775752A - Optical pure diamide compound and its use - Google Patents
Optical pure diamide compound and its use Download PDFInfo
- Publication number
- CN1775752A CN1775752A CN 200510125694 CN200510125694A CN1775752A CN 1775752 A CN1775752 A CN 1775752A CN 200510125694 CN200510125694 CN 200510125694 CN 200510125694 A CN200510125694 A CN 200510125694A CN 1775752 A CN1775752 A CN 1775752A
- Authority
- CN
- China
- Prior art keywords
- alkyl
- diamide compound
- optical pure
- nitrogen
- heteroatomic
- 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.)
- Pending
Links
Landscapes
- Catalysts (AREA)
Abstract
The invention discloses an optical pure diamide compound and its application. And its configuration is L or D shaped, and its basic skeleton is a nitrogen atom-containing 4-8 C heterocycle, and its structural formula contains hydrogen/alkyl (R1), substituent alkyl (R2), and hetero atom-containing alkyl/alkyl whose substituent group contains hetero atom (R3), and the R1 and R2 or the R2 and R3 compose a 3-8 C cycle, and also contains N or O atom (X), carbonyl/tosyl/phosphoryl (Y), and alkyl/substituent alkyl, hetero atom-containing alkyl/alkyl whose substituent group contains hetero atom/ZR4 (where Z is N or O atom). The compound can 3D selectively catalyze hydrogen transfer reduction of imine.
Description
Technical field
The present invention relates to a kind of chiral organic micromolecule compound and the application in asymmetry catalysis thereof, specifically relate to a kind of optical pure diamide compound and application thereof.
Background technology
Many have the active natural and non-natural compound of important biomolecule and all contain the Chiral Amine structural unit, and the reduction of asymmetry catalysis hydrogenation of imines is one of unitary most important method of synthesis of chiral amine structure, and the key of this method is chiral catalyst.At present can high enantioselectivity catalysis hydrogenation of imines reductive catalyzer considerably less, and all be chiral transition metal, these catalyzer not only cost an arm and a leg, easily produce environmental pollution, and its substrate scope of application is also very narrow, and (Synthesis 2004,122,2943; Chem.Rev.2003,103,3029).Therefore develop the asymmetric hydrogenation of imines reducing catalyst with high enantioselectivity and wide application range of substrates, especially synthetic easy, the eco-friendly organic micromolecule catalyst of development is necessary, but also has very big challenge simultaneously.At present the chirality organic catalyst that can be used for catalysis asymmetric hydrogenation reduction imines of bibliographical information only have four examples (Tetrahedron 2001,42,2525; Org.Lett.2004,6,2253 Org.Lett.2005,7,3781; Angew.Chem.Int.Ed.2005,44,7424), the enantioselectivity of its catalytic imines hydrogen transfer reduction reaction is also all also undesirable.
Summary of the invention
One of purpose of the present invention provides a kind of optical pure diamide compound.
Two of purpose of the present invention provides the application of a kind of optical pure diamide compound in asymmetric organic catalytic reaction.
These and other purpose of the present invention will further embody and set forth by following detailed description and explanation.
The present invention is directed to trichlorosilane to the design of the hydrogen transfer reduction of imines with synthesized a series of optical pure diamide organic micromolecule catalysts, and find that it is better than the enantioselectivity and the substrate universality of all similar other chiral organic micromolecule catalysts at present.
The objective of the invention is to realize by following technical proposals:
Optical pure diamide compound of the present invention, its structural formula is as follows:
Be configured as L or D, wherein: Het represents that the basic framework of this compounds is the 4-8 unit heterocycle of nitrogen atom, R
1, R
2And R
3Be respectively hydrogen, alkyl, replacement alkyl, contain heteroatomic alkyl, substituting group contains heteroatomic alkyl, R
1And R
2Or R
2And R
3Become 3-8 unit ring, X is nitrogen or Sauerstoffatom, and Y is carbonic acyl radical, alkylsulfonyl, phosphoryl, R
4For the alkyl of alkyl, replacement, contain heteroatomic alkyl, substituting group contains heteroatomic alkyl or ZR
4(wherein: Z is nitrogen or Sauerstoffatom).
Further, optical pure diamide compound of the present invention, its structural formula is as follows:
Be configured as L or D, wherein: Het represents that the basic framework of this compounds is the 4-8 unit saturated heterocyclic of nitrogen atom, R
1And R
2Be respectively alkyl, replacement alkyl, contain heteroatomic alkyl, substituting group contains heteroatomic alkyl, R
1And R
2Become 3-8 unit ring, R
3Be hydrogen atom, X is nitrogen or Sauerstoffatom, and Y is carbonic acyl radical, alkylsulfonyl, phosphoryl, R
4For the alkyl of alkyl, replacement, contain heteroatomic alkyl, substituting group contains heteroatomic alkyl or ZR
4(wherein: Z is nitrogen or Sauerstoffatom).
What can select is, optical pure diamide compound of the present invention, and its structural formula is as follows:
Be configured as L or D, wherein: Het represents that the basic framework of this compounds is the hexa-atomic saturated heterocyclic of nitrogen atom, R
1And R
2Be phenyl or substituted-phenyl simultaneously, R
3Be hydrogen atom, X is nitrogen or Sauerstoffatom, and Y is a carbonic acyl radical, R
4For the alkyl of alkyl, replacement, contain heteroatomic alkyl, substituting group contains heteroatomic alkyl or ZR
4(wherein: Z is nitrogen or Sauerstoffatom).
In optical pure diamide compound of the present invention; described heterocycle can contain 1-4 heteroatoms, can be at the alkyl of 0-2 carbonic acyl radical of band, alkylsulfonyl, alkyl, replacement except that 1-position and 2-position, contain heteroatomic alkyl or substituting group contains heteroatomic alkyl.Described alkyl can be alkyl, thiazolinyl, alkynyl or aryl.Described alkyl is for containing the alkyl of straight or branched of 1 to 24 carbon atom (being preferably 1-10 carbon atom), as methyl, ethyl, n-propyl, sec.-propyl, isobutyl-, isopentyl, the tertiary butyl or cycloalkyl such as pentamethylene, hexanaphthene; The alkyl that can be replaced by one or more groups, contain at least one carbon atom on heteroatomic alkyl or the alkyl and contained the alkyl that heteroatoms replaces by what heteroatoms replaced.Described thiazolinyl is for the thiazolinyl of the straight or branched that contains two keys at least that contains 1 to 24 carbon atom (being preferably 1-10 carbon atom), the thiazolinyl that can be replaced by one or more groups or contain heteroatomic thiazolinyl or the thiazolinyl that contains the heteroatoms replacement that at least one carbon atom is replaced by heteroatoms, as vinyl, allyl group, n-butene base or isobutenyl.Described alkynyl is for containing the alkynyl that contains a triple-linked straight or branched at least of 1 to 24 carbon atom (being preferably 1-10 carbon atom), as ethynyl, positive butynyl, the alkynyl that can be replaced by one or more groups, contain the alkynyl that contains the heteroatoms replacement that heteroatomic alkynyl or at least one carbon atom are replaced by heteroatoms.Described aryl is that one or more aromatic rings condense aryl together; The aromatic base that is connected with each other; Or the aromatic base that connects by methylene radical, vinyl; Or the geranium crystal that connects as benzophenone, oxygen that connects together by carbonyl, the pentanoic that nitrogen connects.Especially contain one or two aromatic ring condensed or the aromatic nucleus that connects together such as phenyl, naphthyl, phenylbenzene, geranium crystal, pentanoic or similar aryl.Aryl contains 1-200 carbon atom, and representational is 1-50 carbon atom, is more preferably 1-20 carbon atom.The aryl that replaces refers to the aryl that replaced by one or more groups; The aryl that contains the replacement of heteroatoms and heteroatoms refers to the aryl that at least one carbon atom is replaced by heteroatoms.
In optical pure diamide compound of the present invention, Het represents that the basic framework of this compounds is the 4-8 unit heterocycle of nitrogen atom, is preferably saturated heterocyclic, especially piperidine ring and piperazine ring.
Optical pure diamide compound of the present invention, its structural formula is as follows:
Be configured as L or D, wherein: Ph is phenyl or is with substituent phenyl, and X is nitrogen or Sauerstoffatom, R be alkyl, replacement alkyl, contain heteroatomic alkyl or substituting group contains heteroatomic alkyl, being preferably X is Sauerstoffatom, R is a methyl.
Optical pure diamide compound of the present invention can be undertaken immobilized by Ph, R or other group.
The synthetic method of optical purity ring-type diamide compound of the present invention roughly can be divided into following two kinds:
(1) the optical purity cyclic amino acid with protection is a starting raw material, and with corresponding amine condensation, last deprotection also carries out the N-formylation and gets final product.
(2) be starting raw material with the formylated optical purity cyclic amino acid of N-, get final product with corresponding amine condensation.
Concrete synthetic route is as follows:
Optical pure diamide compound of the present invention, stereoselectivity catalysis trichlorosilane reduction imines, reaction scheme is as follows:
Catalyzer is the catalyzer of above-mentioned preparation, wherein R
1, R
2, R
3All can be alkyl, replacement alkyl, contain heteroatomic alkyl or substituting group contains heteroatomic alkyl, be reflected under 0 ℃ or the room temperature and carry out.
The present invention's advantage compared with prior art is: during with the above-mentioned reaction of this catalyst system catalysis, can both obtain enantioselectivity greater than 90% for the vast majority of conventional substrate.And during existing other organic molecule catalyst system catalysis same reaction of the usefulness of reporting on the document (Tetrahedron 2001,42, and 2525; Org.Lett.2004,6,2253; Org.Lett.2005,7,3781; Angew.Chem.Int.Ed.2005,44,7424), only just can obtain enantioselectivity greater than 90% for the several substrates of only a few.
The all raw material of Shi Yonging etc. all is conventional uses in the present invention, can buy from market.In the present invention, refer in particular to as non-, all amount, per-cents are weight unit.
Below in conjunction with embodiment the present invention is carried out concrete description.As known by the technical knowledge, the present invention can realize by other the embodiment that does not break away from its spirit or essential feature.Therefore, following embodiment with regard to each side, all just illustrates, and is not only.All within the scope of the present invention or the change that is equal in the scope of the present invention all be included in the invention.
Embodiment
Embodiment 1: the preparation of compound 1, and structural formula is as follows:
In the 500mL round-bottomed flask, add 200mL exsiccant methylene dichloride, be chilled to 0 ℃, add L-Boc-proline(Pro) (4.3g, 20.0mmol), (1S, 2R)-(-)-2-amino-1,2-phenylbenzene-1-acetyl oxidative ethane (6.1g, 24.0mmol), N-hydroxybenzotriazole (3.5g, 24.0mmol), N, N-diisopropyl ethyl amine (DIEA, 7.0mL, 40.0mmol), EDCI (4.60g, 24.0mmol).Stirring at room 12 hours, concentrating under reduced pressure.With the dilution of 400mL ethyl acetate, use saturated sodium bicarbonate (100mL) successively, 1N hydrochloric acid (100mL), saturated sodium-chloride (100mL) is washed, and anhydrous sodium sulfate drying filters.Concentrate back column chromatography (sherwood oil: ethyl acetate=1: 1).The solid that obtains is dissolved in the solution of 200mL trifluoracetic acid and methylene dichloride (V/V, 1: 2), stirring at room 30 minutes, and decompression concentrates down.With the saturated sodium bicarbonate neutralization, ethyl acetate extraction (300mL * 3) merges organic layer, and saturated sodium-chloride (100mL) is washed, and anhydrous sodium sulfate drying filters, and concentrates.The solid that obtains is dissolved in formic acid (50mL) at 0 ℃, slowly drips acetic anhydride (12mL), stirring at room 12 hours, (the methylene dichloride: methyl alcohol=25: 1), obtain white solid, yield: 65% of column chromatography behind the reaction solution concentrating under reduced pressure, m.p.142.0-143.0 ℃, [α]
D 20=-53.0 (c=0.100, CH
3CH
2OH);
1HNMR (600MHz, CDCl
3): δ (ppm) 1.77-1.90 (m, 3H), 2.05 (s, 3H), 2.48-2.53 (m, 1H), and 3.32-3.36 (m, 1H), 3.46-3.49 (m, 1H), 4.48 (d, J=6.00Hz, 1H), 5.38 (dd, J=3.18Hz, 9.00Hz, 1H), 6.07 (d, J=6.00Hz, 1H), 7.13-7.16 (m, 4H), 7.19-7.31 (m, 6H), 8.08 (d, J=8.58Hz, 1H), 8.19 (s, 1H);
13CNMR (150MHz, CDCl
3): δ (ppm) 20.9,22.6,23.9,26.4,46.7,57.7,57.8,126.6,126.9,127.2,127.7,128.1,128.5,137.3,138.2,162.5,169.6,169.9; ESI HRMS (C
22H
24N
2O
4+ Na)
+Theoretical value m/z 403.1628, measured value m/z 403.1618.
Embodiment 2: the preparation of compound 2, and structural formula is as follows:
In the 500mL round-bottomed flask, add 200mL exsiccant methylene dichloride, be chilled to 0 ℃, add L-Boc-proline(Pro) (4.3g, 20.0mmol), (1R, 2S)-(-)-2-amino-1,2-phenylbenzene-1-acetyl oxidative ethane (6.1g, 24.0mmol), N-hydroxybenzotriazole (3.5g, 24.0mmol), N, N-diisopropyl ethyl amine (DIEA, 7.0mL, 40.0mmol), EDCI (4.60g, 24.0mmol).Stirring at room 12 hours, aftertreatment and subsequent reactions are with embodiment 1.Obtain white solid, yield: 70%, m.p.178.0-181.0 ℃, [α]
D 20=-39.0 (c=0.100, CH
3CH
2OH);
1HNMR (600MHz, CDCl
3): δ (ppm) 1.81-1.96 (m, 3H), 2.11 (s, 3H), 2.48-2.51 (m, 1H), and 3.38-3.42 (m, 1H), 3.51-3.55 (m, 1H), 4.53 (d, J=7.92Hz, 1H), 5.38 (dd, J=5.04Hz, 9.06Hz, 1H), 6.10 (d, J=4.8Hz, 1H), and 7.02-7.30 (m, 10H), 8.06 (d, J=9.06Hz, 1H), 8.26 (s, 1H);
13CNMR (150MHz, CDCl
3): δ (ppm) 21.0,21.1,24.1,26.3,46.9,57.3,57.8,127.0,127.6,127.8,128.1,128.1,128.2,136.3,137.1,162.5,169.3,170.1; ESI HRMS (C
22H
24N
2O
4+ Na)
+Theoretical value m/z 403.1628, measured value m/z403.1616.
Embodiment 3: the preparation of compound 3, and structural formula is as follows:
In the 500mL round-bottomed flask, add 200mL exsiccant methylene dichloride, be chilled to 0 ℃, add (S)-2-carboxylic acid-Boc-azetidine (2.0g, 20.0mmol), (1R, 2S)-(-)-2-amino-1,2-phenylbenzene-1-acetyl oxidative ethane (6.1g, 24.0mmol), N-hydroxybenzotriazole (3.5g, 24.0mmol), N, N-diisopropyl ethyl amine (DIEA, 7.0mL, 40.0mmol), EDCI (4.60g, 24.0mmol).Stirring at room 12 hours, aftertreatment and subsequent reactions are with embodiment 1.Obtain the finished product, yield: 60%,
Embodiment 4: the preparation of compound 4, and structural formula is as follows:
In the 500mL round-bottomed flask, add 200mL exsiccant methylene dichloride, be chilled to 0 ℃, add L-Boc-proline(Pro) (4.3g, 20.0mmol), (1R, 2R)-(-)-2-amino-1,2-phenylbenzene-1-acetyl oxidative ethane (6.1g, 24.0mmol), N-hydroxybenzotriazole (3.5g, 24.0mmol), N, N-diisopropyl ethyl amine (DIEA, 7.0mL, 40.0mmol), EDCI (4.60g, 24.0mmol).Stirring at room 12 hours, aftertreatment and subsequent reactions are with embodiment 1.Obtain white solid, yield: 63%, m.p.59.0-63.0 ℃; [α]
D 20=-92.0 (c=0.100, CH
3CH
2OH);
1HNMR (600MHz, CDCl
3): δ (ppm) 1.79-1.87 (m, 3H), 2.07 (s, 3H), 2.40-2.44 (m, 1H), and 3.32-3.36 (m, 1H), 3.52-3.55 (m, 1H), 4.53 (d, J=7.62Hz, 1H), 5.38 (dd, J=5.64Hz, 8.64Hz, 1H), 6.06 (d, J=5.64Hz, 1H), and 7.12-7.25 (m, 10H), 8.03 (d, J=8.82Hz, 1H), 8.32 (s, 1H);
13CNMR (150MHz, CDCl
3): δ (ppm) 20.9,22.6,23.9,26.4,46.7,57.7,57.9,126.6,126.9,127.6,128.1,128.5,128.6,137.7,138.2,162.5,169.6,169.9; ESI HRMS (C
22H
24N
2O
4+ Na)
+Theoretical value m/z 403.1628, measured value m/z403.1647.
Embodiment 5: the preparation of compound 5, and structural formula is as follows:
In the 500mL round-bottomed flask, add 200mL exsiccant methylene dichloride, be chilled to 0 ℃, add L-Boc-proline(Pro) (4.3g, 20.0mmol), (1S, 2S)-(-)-2-amino-1,2-phenylbenzene-1-acetyl oxidative ethane (6.1g, 24.0mmol), N-hydroxybenzotriazole (3.5g, 24.0mmol), N, N-diisopropyl ethyl amine (DIEA, 7.0mL, 40.0mmol), EDCI (4.60g, 24.0mmol).Stirring at room 12 hours, aftertreatment and subsequent reactions are with embodiment 1.Obtain white solid, yield: 72%, m.p.61.0-65.0 ℃, [α]
D 20=-16.0 (c=0.100, CH
3CH
2OH);
1HNMR (600MHz, CDCl
3): δ (ppm) 1.80-1.88 (m, 1H), 1.91-1.96 (m, 2H), 2.11 (s, 3H), and 2.32-2.36 (m, 1H), 3.45-3.49 (m, 1H), 3.55-3.59 (m, 1H), 4.51 (d, J=7.98Hz, 1H), 5.33 (dd, J=5.94Hz, 8.70Hz, 1H), 6.02 (d, J=5.94Hz, 1H), 7.10-7.30 (m, 10H), 8.02 (d, J=8.76Hz, 1H), 8.34 (s, 1H);
13CNMR (150MHz, CDCl
3): δ (ppm) 21.0,22.9,26.8,30.3,46.9,57.8,58.1,126.7,127.1,127.6,128.2,128.3,128.4,137.2,138.5,162.4,169.6,170.3; ESI HRMS (C
22H
24N
2O
4+ Na)
+Theoretical value m/z403.1628, measured value m/z 403.1621.
Embodiment 6: the preparation of compound 6, and structural formula is as follows:
In the 500mL round-bottomed flask, add 200mL exsiccant methylene dichloride, be chilled to 0 ℃, add (S)-2-carboxylic acid-Boc-azepan (4.9g, 20.0mmol), (1S, 2S)-(-)-2-amino-1,2-phenylbenzene-1-acetyl oxidative ethane (6.1g, 24.0mmol), N-hydroxybenzotriazole (3.5g, 24.0mmol), N, N-diisopropyl ethyl amine (DIEA, 7.0mL, 40.0mmol), EDCI (4.60g, 24.0mmol).Stirring at room 12 hours, aftertreatment and subsequent reactions are with embodiment 1.Obtain the finished product, yield: 70%.
Embodiment 7: the preparation of compound 7, and structural formula is as follows:
In the 500mL round-bottomed flask, add 200mL exsiccant methylene dichloride, be chilled to 0 ℃, add L-Boc-proline(Pro) (4.3g, 20.0mmol), quadrol (0.54g, 18.0mmol), N-hydroxybenzotriazole (3.5g, 24.0mmol), N, N-diisopropyl ethyl amine (DIEA, 7.0mL, 40.0mmol), EDCI (4.60g, 24.0mmol).Stirring at room 12 hours, concentrating under reduced pressure.With the dilution of 400mL ethyl acetate, use saturated sodium bicarbonate (100mL) successively, 1N hydrochloric acid (100mL), saturated sodium-chloride (100mL) is washed, and anhydrous sodium sulfate drying filters, and is dissolved in the methylene dichloride recrystallization.The solid that obtains is dissolved in the solution of 200mL trifluoracetic acid and methylene dichloride (V/V, 1: 2), stirring at room 30 minutes.Add 100mL toluene in reaction solution, decompression concentrates down.By Zeo-karb (ammoniacal liquor of 3.0M), (methylene dichloride: methyl alcohol=10: 1) of column chromatography behind the concentrating under reduced pressure.The product that obtains is dissolved in formic acid (50mL) at 0 ℃, slowly drips acetic anhydride (12mL), stirring at room 12 hours, column chromatography behind the reaction solution concentrating under reduced pressure (methylene dichloride: methyl alcohol=25: 1), obtain thick liquid, yield: 69%,
1HNMR (600MHz, CD
3OD): δ (ppm) 1.87-2.08 (m, 3H), 2.22-2.29 (m, 1H), 3.31-3.36 (m, 2H), 3.64-3.71 (m, 2H), 4.26-4.30 (m, 1H), 8.25 (s, 1H);
13CNMR (150MHz, CD
3OD): δ (ppm) 23.7,29.6,38.6,44.0,58.2,162.3,172.8; ESI HRMS (C
14H
22N
4O
4+ Na)
+Theoretical value m/z 333.1533, measured value m/z 333.1522.
Embodiment 8: the preparation of compound 8, and structural formula is as follows:
In the 500mL round-bottomed flask, add 200mL exsiccant methylene dichloride, be chilled to 0 ℃, add (S)-2-carboxylic acid-Boc-azetidine (2.0g, 20.0mmol), quadrol (0.54g, 18.0mmol), N-hydroxybenzotriazole (3.5g, 24.0mmol), N, N-diisopropyl ethyl amine (DIEA, 7.0mL, 40.0mmol), EDCI (4.60g, 24.0mmol).Stirring at room 12 hours, aftertreatment and reaction are with embodiment 7.Obtain the finished product, yield: 67%.
Embodiment 9: the preparation of compound 9, and structural formula is as follows:
In the 500mL round-bottomed flask, add 200mL exsiccant methylene dichloride, be chilled to 0 ℃, add L-Boc-proline(Pro) (4.3g, 20.0mmol), (1S, 2S)-cyclohexanediamine (1.0g, 18.0mmol), the N-hydroxybenzotriazole (3.5g, 24.0mmol), N, the N-diisopropyl ethyl amine (DIEA, 7.0mL, 40.0mmol), EDCI (4.60g, 24.0mmol).Stirring at room 12 hours, aftertreatment and reaction are with embodiment 7.Obtain white solid, yield: 62%, m.p.240.0-241.0 ℃, [α]
D 20=-148.28 (c=0.160, CH
3CH
2OH),
1HNMR (600MHz, CD
3OD): δ (ppm) 1.29-1.39 (m, 4H), 1.78-2.27 (m, 12H), 3.45-3.71 (m, 6H), 4.25-4.44 (m, 2H), 8.23 (s, 2H);
13CNMR (150MHz, CD
3OD): δ (ppm) 22.5,23.7,24.3,29.7,30.2,31.7,44.0,46.7,52.7,52.8,58.2,60.6,162.2,163.3,172.7,172.4.
Embodiment 10: the preparation of compound 10, and structural formula is as follows:
In the 500mL round-bottomed flask, add 200mL exsiccant methylene dichloride, be chilled to 0 ℃, add L-Boc-nipecotic acid (4.6g, 20.0mmol), (1S, 2S)-(-)-2-amino-1,2-phenylbenzene-1-acetyl oxidative ethane (6.1g, 24.0mmol), N-hydroxybenzotriazole (3.5g, 24.0mmol), N, N-diisopropyl ethyl amine (DIEA, 7.0mL, 40.0mmol), EDCI (4.60g, 24.0mmol).Stirring at room 12 hours, aftertreatment and reaction are with embodiment 1.Obtain white solid, yield: 72%,
1HNMR (600MHz, CDCl
3): δ (ppm) 1.36-1.49 (m, 2H), 1.50-1.55 (m, 1H), 1.63-1.68 (m, 2H), 2.10 (s, 3H), 2.14 (d, J=13.32Hz, 1H), and 3.09-3.14 (m, 1H), 3.53 (d, J=9.84Hz, 1H), 4.98 (d, J=5.58Hz, 1H), 5.29-5.33 (m, 1H), 6.02 (d, J=6.54Hz, 1H), 7.01-7.28 (m, 10H), 8.17 (s, 1H);
13CNMR (150MHz, CDCl
3): δ (ppm) 20.9,21.2,25.1,25.5,44.4,50.9,58.1,126.7,127.0,127.7,128.3,128.5,128.6,136.8,138.5,162.6,169.4,170.6; ESI HRMS (C
23H
26N
2O
4+ Na)
+Theoretical value m/z 417.1785, measured value m/z 417.1800.
Embodiment 11: the preparation of compound 11, and structural formula is as follows:
In the 500mL round-bottomed flask, add 200mL exsiccant methylene dichloride, be chilled to 0 ℃, add L-Boc-nipecotic acid (4.6g, 20.0mmol), (1S, 2S)-(-)-2-amino-1,2-phenylbenzene-ethanamide ethane (6.1g, 24.0mmol), N-hydroxybenzotriazole (3.5g, 24.0mmol), N, N-diisopropyl ethyl amine (DIEA, 7.0mL, 40.0mmol), EDCI (4.60g, 24.0mmol).Stirring at room 12 hours, aftertreatment and reaction are with embodiment 1.Obtain final product, yield 72%.
Embodiment 12: the preparation of compound 12, and structural formula is as follows:
In the 500mL round-bottomed flask, add 200mL exsiccant methylene dichloride, be chilled to 0 ℃, add L-Boc-nipecotic acid (4.6g, 20.0mmol), (1S, 2S)-(-)-2-amino-1,2-phenylbenzene-sulfonyloxy methyl oxidative ethane (7.0g, 24.0mmol), N-hydroxybenzotriazole (3.5g, 24.0mmol), N, N-diisopropyl ethyl amine (DIEA, 7.0mL, 40.0mmol), EDCI (4.60g, 24.0mmol).Stirring at room 12 hours, aftertreatment and reaction are with embodiment 1.Obtain final product, yield: 75%.
Embodiment 13: the preparation of compound 13, and structural formula is as follows:
In the 500mL round-bottomed flask, add 200mL exsiccant methylene dichloride, be chilled to 0 ℃, add L-Boc-nipecotic acid (4.6g, 20.0mmol), (1R, 2S)-(-)-2-amino-1,2-phenylbenzene-acetyl oxidative ethane (6.1g, 24.0mmol), N-hydroxybenzotriazole (3.5g, 24.0mmol), N, N-diisopropyl ethyl amine (DIEA, 7.0mL, 40.0mmol), EDCI (4.60g, 24.0mmol).Stirring at room 12 hours, aftertreatment and reaction are with embodiment 1.Obtain white solid, yield: 66%, m.p.62-64 ℃, [α]
D 20=-31.4 (c=0.137, EtOH);
1H NMR (600MHz, CDCl
3): δ (ppm) 1.33-1.74 (m, 5H), 2.07 (s, 3H), 2.15 (d, J=13.62Hz, 1H), 3.01 (dt, J=2.70,13.02Hz, 1H), 3.43 (dd, J=3.06,13.26Hz, 1H), 4.98 (d, J=5.82Hz, 1H), 5.43 (dd, J=5.1Hz, 8.88Hz, 1H), 6.07 (d, J=5.28Hz, 1H), 6.84 (m, 1H), 7.01 (m, 2H), 7.07 (m, 2H), 7.11-7.14 (m, 1H), 7.24-7.26 (m, 4H), 7.29 (m, 1H), 8.12 (s, 1H);
13CNMR (150MHz, CDCl
3): δ (ppm) 20.8,21.0,24.9,25.5,26.7,44.3,50.8,56.7,127.1,127.4,127.8,128.2,128.3,128.4,135.8,137.4,162.6,169.3; ESI HRMSexact mass calcd.for (C
23H
26N
2O
4+ Na)
+Theoretical value m/z417.1785, measured value m/z417.1791.
Embodiment 14: the preparation of compound 14, and structural formula is as follows:
In the 500mL round-bottomed flask, add 200mL exsiccant methylene dichloride, be chilled to 0 ℃, add L-Boc-nipecotic acid (4.6g, 20.0mmol), (S)-and 2-amino-2-phenyl-acetyl oxidative ethane (4.3g, 24.0mmol), N-hydroxybenzotriazole (3.5g, 24.0mmol), N, N-diisopropyl ethyl amine (DIEA, 7.0mL, 40.0mmol), EDCI (4.60g, 24.0mmol).Stirring at room 12 hours, aftertreatment and reaction are with embodiment 1.Obtain the finished product, yield: 78%.
Embodiment 15: the preparation of compound 15, and structural formula is as follows:
(15)
In the 500mL round-bottomed flask, add 200mL exsiccant methylene dichloride, be chilled to 0 ℃, add L-Boc-nipecotic acid (4.6g, 20.0mmol), (1S, 2R)-(-)-2-amino-1,2-phenylbenzene-acetyl oxidative ethane (6.1g, 24.0mmol), N-hydroxybenzotriazole (3.5g, 24.0mmol), N, N-diisopropyl ethyl amine (DIEA, 7.0mL, 40.0mmol), EDCI (4.60g, 24.0mmol).Stirring at room 12 hours, aftertreatment and reaction are with embodiment 1.Obtain white solid, yield: 69%, m.p.63-66 ℃, [α]
D 20=-62.1 (c=0.116, EtOH);
1H NMR (600MHz, CDCl
3): δ (ppm) 1.31-1.89 (m, 5H), 1.99 (s, 3H), 2.16 (d, J=14.0Hz, 1H), 2.65 (dt, J=2.88,13.20Hz, 1H), 3.32 (d, J=13.4Hz, 1H), 4.84 (d, J=5.7Hz, 1H), 5.43 (dd, J=6.84,8.94Hz, 1H), 6.06 (d, J=6.72Hz, 1H), 6.88 (d, J=9.18Hz, 1H), 7.10-7.22 (m, 4H), 7.26-7.33 (m, 6H), 7.96 (s, 1H);
13CNMR (150MHz, CDCl
3): δ (ppm) 20.8,21.0,24.4,25.4,26.6,44.1,50.6,56.4,127.4,127.6,127.9,128.3,128.4,128.5,136.7,137.4,162.8,169.0; ESI HRMS exact mass calcd.for (C
23H
26N
2O
4+ Na)
+Theoretical value m/z 417.1785, measured value m/z 417.1801.
Embodiment 16: the preparation of compound 16, and structural formula is as follows:
In the 500mL round-bottomed flask, add 200mL exsiccant methylene dichloride, be chilled to 0 ℃, add L-Boc-nipecotic acid (4.6g, 20.0mmol), (1S, 2R)-(-)-2-amino-1,2-phenylbenzene-phenylbenzene see acyl-oxygen ethane (9.9g, 24.0mmol), N-hydroxybenzotriazole (3.5g, 24.0mmol), N, N-diisopropyl ethyl amine (DIEA, 7.0mL, 40.0mmol), EDCI (4.60g, 24.0mmol).Stirring at room 12 hours, aftertreatment and reaction are with embodiment 1.Obtain the finished product, yield: 73%,
Embodiment 17: the preparation of compound 17, and structural formula is as follows:
In the 500mL round-bottomed flask, add 200mL exsiccant methylene dichloride, be chilled to 0 ℃, add L-Boc-benzo nipecotic acid (5.5g, 20.0mmol), quadrol (0.54g, 18.0mmol), N-hydroxybenzotriazole (3.5g, 24.0mmol), N, N-diisopropyl ethyl amine (DIEA, 7.0mL, 40.0mmol), EDCI (4.60g, 24.0mmol).Stirring at room 12 hours, aftertreatment and reaction are with embodiment 7.Obtain white solid, yield: 75%,
1HNMR (600MHz, CDCl
3): δ (ppm) 3.07-3.17 (m, 1H), 3.20-3.27 (m, 1H), 3.28-3.32 (m, 1H), 3.41-3.49 (m, 1H), 4.48-4.61 (m, 3H), 7.12-7.16 (m, 1H), 7.18-7.19 (m, 1H), 7.21-7.28 (m, 2H), 8.28 (s, 1H).
Embodiment 18: the preparation of compound 18, and structural formula is as follows:
In the 500mL round-bottomed flask, add 200mL exsiccant methylene dichloride, be chilled to 0 ℃, add L-Boc-proline(Pro) (4.3g, 20.0mmol), N-acetyl quadrol (2.4g, 24.0mmol), N-hydroxybenzotriazole (3.5g, 24.0mmol), N, N-diisopropyl ethyl amine (DIEA, 7.0mL, 40.0mmol), EDCI (4.60g, 24.0mmol).Stirring at room 12 hours, aftertreatment and reaction are with embodiment 1.Get thick liquid, yield: 60%, [α]
D 20=-52.32 (c=0.516, CH
3CH
2OH),
1HNMR (600MHz, CD
3OD): δ (ppm) 1.86-2.09 (m, 6H), 2.21-2.30 (m, 1H), 3.24-3.34 (m, 6H), 3.47-3.72 (m, 2H), 4.28 (dd, J=5.64Hz, 8.52Hz, 1H), 8.25 (s, 1H);
13CNMR (150MHz, CD
3OD): δ (ppm) 21.2,23.7,29.7,38.4,38.8,46.8,58.2,162.3,172.4,172.9.
Embodiment 19: the preparation of compound 19, and structural formula is as follows:
In the 500mL round-bottomed flask, add 200mL exsiccant methylene dichloride, be chilled to 0 ℃, add (S)-2-carboxylic acid-Boc-Azacyclooctane (5.1g, 20.0mmol), N-acetyl quadrol (2.4g, 24.0mmol), N-hydroxybenzotriazole (3.5g, 24.0mmol), N, N-diisopropyl ethyl amine (DIEA, 7.0mL, 40.0mmol), EDCI (4.60g, 24.0mmol).Stirring at room 12 hours, aftertreatment and reaction are with embodiment 1.Get the finished product, yield: 70%
Embodiment 20: the preparation of compound 20, and structural formula is as follows:
In the 500mL round-bottomed flask, add 200mL exsiccant methylene dichloride, be chilled to 0 ℃, add L-Boc-proline(Pro) (4.3g, 20.0mmol), N-formyl quadrol (2.1g, 24.0mmol), N-hydroxybenzotriazole (3.5g, 24.0mmol), N, N-diisopropyl ethyl amine (DIEA, 7.0mL, 40.0mmol), EDCI (4.60g, 24.0mmol).Stirring at room 12 hours, aftertreatment and reaction are with embodiment 1.Get thick liquid, yield: 62%, [α]
D 20=-46.88 (c=0.128, CH
3CH
2OH),
1HNMR (600MHz, CD
3OD): δ (PPm) 1.87-2.10 (m, 3H), 2.22-2.31 (m, 1H), 3.27-3.38 (m, 4H), 3.47-3.72 (m, 2H), 4.30 (dd, J=4.86Hz, 8.52Hz, 1H), 8.08 (d, J=5.82Hz, 1H), 8.26 (s, 1H);
13CNMR (150MHz, CD
3OD): δ (ppm) 23.7,29.7,36.9,38.7,46.7,58.2,162.3,162.8,172.9.
Embodiment 21: the preparation of compound 21, and structural formula is as follows:
In the 500mL round-bottomed flask, add 200mL exsiccant methylene dichloride, be chilled to 0 ℃, add L-Boc-4-(4 '-tertiary butyl) benzenesulfonyl piperazine acid (8.5g; 20.0mmol), (1S, 2S)-(-)-2-amino-1; 2-phenylbenzene-acetyl oxidative ethane (6.1g, 24.0mmol), N-hydroxybenzotriazole (3.5g; 24.0mmol), N, N-diisopropyl ethyl amine (DIEA; 7.0mL; 40.0mmol), EDCI (4.60g, 24.0mmol).Stirring at room 12 hours, aftertreatment and reaction are with embodiment 1.Get white solid, yield: 62%,
1HNMR (600MHz, CDCl
3) δ (ppm) 1.34 (s, 9H), 2.04 (s, 3H), 222-2.32 (m, 1H), and 2.30-2.40 (m, 2H), 3.05-3.09 (dt, J=13.2Hz, 1H), and 4.07-4.20 (m, 2H), 5.47-5.51 (m, 1H), 6.17-6.18 (d, J=6.90,1H), 7.14-7.18 (m, 2H), 7.25-7.35 (m, 8H), 7.53-7.57 (m, 2H), 7.65-7.68 (m, 2H), 8.01 (s, 1H).
Embodiment 22: the preparation of compound 22, and structural formula is as follows:
In the 500mL round-bottomed flask, add 200mL exsiccant methylene dichloride, be chilled to 0 ℃, add L-Boc-4-benzyl diethylenediamine acid (6.4g, 20.0mmol), the glycyl oxidative ethane (2.4g, 24.0mmol), N-hydroxybenzotriazole (3.5g, 24.0mmol), N, N-diisopropyl ethyl amine (DIEA, 7.0mL, 40.0mmol), EDCI (4.60g, 24.0mmol).Stirring at room 12 hours, aftertreatment and reaction are with embodiment 1.Get the finished product, yield: 60%.
Embodiment 23: the preparation of compound 23, and structural formula is as follows:
In the 500mL round-bottomed flask, add 200mL exsiccant methylene dichloride, be chilled to 0 ℃, add L-Boc-4-benzoyl-piperazine acid (6.68g; 20.0mmol), (S)-and 2-amino-2-phenyl-acetyl oxidative ethane (4.3g, 24.0mmol); N-hydroxybenzotriazole (3.5g; 24.0mmol), N, N-diisopropyl ethyl amine (DIEA; 7.0mL; 40.0mmol), EDCI (4.60g, 24.0mmol).Stirring at room 12 hours, aftertreatment and reaction are with embodiment 1.Obtain the finished product, yield: 71%.
Embodiment 24: the preparation of compound 24, and structural formula is as follows:
In the 500mL round-bottomed flask, add 200mL exsiccant methylene dichloride, be chilled to 0 ℃, add L-Boc-4-ethanoyl piperazine acid (5.44g; 20.0mmol), (S)-and 2-phenyl-N-benzoyl quadrol (5.76g, 24.0mmol); N-hydroxybenzotriazole (3.5g; 24.0mmol), N, N-diisopropyl ethyl amine (DIEA; 7.0mL; 40.0mmol), EDCI (4.60g, 24.0mmol).Stirring at room 12 hours, aftertreatment and reaction are with embodiment 1.Obtain the finished product, yield: 71%.
Embodiment 25-42: chiral catalyst 11 catalytic asymmetric imines reduction reactions
Pack in the tool plug test tube of 5mL catalyzer 11 (0.05mmol), imines (0.5mmol) add methylene dichloride 2mL, are chilled to 0 ℃, stir to add SiHCl down
3(100ul, 2eq), temperature rises to room temperature, reacts 16 hours.With the cancellation of 2mL saturated sodium bicarbonate, ethyl acetate extraction (20mL * 3), anhydrous magnesium sulfate drying filters column chromatography (sherwood oil: ethyl acetate=40: 1) obtain N-(1-phenylethyl) aniline, the results are shown in following table.
| Embodiment | Imines (R 1，R 2) | Yield [%] | ee[％] | Literature value ee[%] |
| 25 26 27 28 29 30 31 32 33 34 35 36 36 38 39 40 41 42 | Ph，Ph 4-CF 3Ph，Ph 4-NO 2Ph，Ph 4-BrPh，Ph 3-BrPh，Ph 2-ClPh，Ph 4-MeOPh，Ph 2-Naphthyl，Ph 6-MeONaphthyl，Ph Cyclohexyl，Ph Ph，4-MeOPh Ph，4-MePh Ph，2-MeOPh Ph，4-ClPh Ph，2-ClPh Ph，4-BrPh Cyclohexyl，4-BrPh Cyclohexyl，2-OMePh | 97 85 96 98 82 86 95 92 91 81 98 90 92 98 93 91 80 75 | 95 96 95 95 94 87 93 93 90 95 92 95 89 93 90 93 95 87 | 55 a，92 b，72 c 87 b，70 c 49 a，85 b --- --- --- 85 b 66 a，87 b，68 c --- 37 b 91 b，70 c，88 d --- 22 b --- --- --- --- --- |
a)F.Iwasaki，et al Tetrahedron Lett.20011，42，2525；b)A.V.Malkov，et al.Org.Lett.2004，6，2253；c)M.Rueping，et al.Org.Lett.2005，7，3781；d)S.Hoffmann，et al.Angew.Chem.Int.Ed.2005，44，7424.
Embodiment 43: chiral catalyst 13 catalytic asymmetric imines reduction reactions
In the tool plug test tube of 5mL, pack into catalyzer 13 (19.7mg, 0.05mmol), (97.5mg 0.5mmol), adds methylene dichloride 2mL to imines, is chilled to 0 ℃, stirs to add SiHCl down
3(100ul, 2eq), temperature rises to room temperature, reacts 16 hours.With the cancellation of 2mL saturated sodium bicarbonate, ethyl acetate extraction (20mL * 3), anhydrous magnesium sulfate drying filters, column chromatography (sherwood oil: ethyl acetate=40: 1 obtains N-(1-phenylethyl) aniline, yield: 98%, and ee:93%.This reaction of known small molecules catalyst (Tetrahedron 2001,42,2525) yield: 97%, ee:55%.
Embodiment 44: chiral catalyst 5 catalytic asymmetric imines reduction reactions
In the tool plug test tube of 5mL, pack into catalyzer 5 (19.0mg, 0.05mmol), (97.5mg 0.5mmol), adds methylene dichloride 2mL to imines, is chilled to 0 ℃, stirs to add SiHCl down
3(100ul, 2eq), temperature rises to room temperature, reacts 16 hours.With the cancellation of 2mL saturated sodium bicarbonate, ethyl acetate extraction (20mL * 3), anhydrous magnesium sulfate drying filters, column chromatography (sherwood oil: ethyl acetate=40: 1 obtains N-(1-phenylethyl) aniline, yield: 90%, and ee:80%.
Embodiment 45: chiral catalyst 7 catalytic asymmetric imines reduction reactions
In the tool plug test tube of 5mL, pack into catalyzer 7 (15.5mg, 0.05mmol), (97.5mg 0.5mmol), adds methylene dichloride 2mL to imines, is chilled to 0 ℃, stirs to add SiHCl down
3(100ul, 2eq), temperature rises to room temperature, reacts 16 hours.With the cancellation of 2mL saturated sodium bicarbonate, ethyl acetate extraction (20mL * 3), anhydrous magnesium sulfate drying filters, column chromatography (sherwood oil: ethyl acetate=40: 1) obtain N-(1-phenylethyl) aniline, yield: 95%, ee:77%.
Embodiment 46: chiral catalyst 21 catalytic asymmetric imines reduction reactions
In the tool plug test tube of 5mL, pack into catalyzer 21 (29.6mg, 0.05mmol), (105mg 0.5mmol), adds methylene dichloride 2mL to imines, is chilled to 0 ℃, stirs to add SiHCl down
3(100ul, 2eq), temperature rises to room temperature, reacts 16 hours.With the cancellation of 2mL saturated sodium bicarbonate, ethyl acetate extraction (20mL * 3), anhydrous magnesium sulfate drying filters, column chromatography (sherwood oil: ethyl acetate=40: 1 obtains N-(1-phenyl propyl) aniline, yield: 96%, and ee:90%.
Embodiment 47: chiral catalyst 13 catalytic asymmetric imines reduction reactions
In the tool plug test tube of 5mL, pack into catalyzer 13 (19.7mg, 0.05mmol), (87.5mg 0.5mmol), adds methylene dichloride 2mL to imines, is chilled to 0 ℃, stirs to add SiHCl down
3(100ul, 2eq), temperature rises to room temperature, reacts 16 hours.With the cancellation of 2mL saturated sodium bicarbonate, ethyl acetate extraction (20mL * 3), anhydrous magnesium sulfate drying filters, column chromatography (sherwood oil: ethyl acetate=40: 1 obtains N-(2-methyl amyl) aniline, yield: 82%, and ee:78%.
Embodiment 48: chiral catalyst 13 catalytic asymmetric imines reduction reactions
In the tool plug test tube of 5mL, pack into catalyzer 13 (19.7mg, 0.05mmol), (120mg 0.5mmol), adds methylene dichloride 2mL to imines, is chilled to 0 ℃, stirs to add SiHCl down
3(100ul, 2eq), temperature rises to room temperature, reacts 16 hours.With the cancellation of 2mL saturated sodium bicarbonate, ethyl acetate extraction (20mL * 3), anhydrous magnesium sulfate drying filters, column chromatography (sherwood oil: ethyl acetate=10: 1) obtain N-(1-p-nitrophenyl ethyl) aniline, yield: 96%, ee:91%.
Embodiment 49: chiral catalyst 7 catalytic asymmetric imines reduction reactions
In the tool plug test tube of 5mL, pack into catalyzer 7 (15.5mg, 0.05mmol), (112.5mg 0.5mmol), adds methylene dichloride 2mL to imines, is chilled to 0 ℃, stirs to add SiHCl down
3(100ul, 2eq), temperature rises to room temperature, reacts 16 hours.With the cancellation of 2mL saturated sodium bicarbonate, ethyl acetate extraction (20mL * 3), anhydrous magnesium sulfate drying filters, column chromatography (sherwood oil: ethyl acetate=40: 1) obtain N-(1-o-methoxyphenyl ethyl) aniline, yield: 75%, ee:78%.
Embodiment 50: chiral catalyst 13 catalytic asymmetric imines reduction reactions
In the tool plug test tube of 5mL, pack into catalyzer 13 (19.7mg, 0.05mmol), (137mg 0.5mmol), adds methylene dichloride 2mL to imines, is chilled to 0 ℃, stirs to add SiHCl down
3(100ul, 2eq), temperature rises to room temperature, reacts 16 hours.With the cancellation of 2mL saturated sodium bicarbonate, ethyl acetate extraction (20mL * 3), anhydrous magnesium sulfate drying filters, column chromatography (sherwood oil: ethyl acetate=40: 1 obtains N-(bromophenyl ethyl between 1-) aniline, yield: 80%, and ee:92%.
Embodiment 51: chiral catalyst 13 catalytic asymmetric imines reduction reactions
In the tool plug test tube of 5mL, pack into catalyzer 13 (19.7mg, 0.05mmol), (115.0mg 0.5mmol), adds methylene dichloride 2mL to imines, is chilled to 0 ℃, stirs to add SiHCl down
3(100ul, 2eq), temperature rises to room temperature, reacts 16 hours.With the cancellation of 2mL saturated sodium bicarbonate, ethyl acetate extraction (20mL * 3), anhydrous magnesium sulfate drying filters, column chromatography (sherwood oil: ethyl acetate=obtain N-(1-phenylethyl) to first chloroaniline, yield at 40: 1: 95%, ee:92%.
Embodiment 52: chiral catalyst 5 catalytic asymmetric imines reduction reactions
In the tool plug test tube of 5mL, pack into catalyzer 5 (19.0mg, 0.05mmol), (120mg 0.5mmol), adds methylene dichloride 2mL to imines, is chilled to 0 ℃, stirs to add SiHCl down
3(100ul, 2eq), temperature rises to room temperature, reacts 16 hours.With the cancellation of 2mL saturated sodium bicarbonate, ethyl acetate extraction (20mL * 3), anhydrous magnesium sulfate drying filters, column chromatography (sherwood oil: ethyl acetate=10: 1) obtain N-(1-phenylethyl), yield to nitro base aniline: 90%, ee:76%.
Embodiment 53: chiral catalyst 21 catalytic asymmetric imines reduction reactions
In the tool plug test tube of 5mL, pack into catalyzer 21 (29.6mg, 0.05mmol), (122.5mg 0.5mmol), adds methylene dichloride 2mL to imines, is chilled to 0 ℃, stirs to add SiHCl down
3(100ul, 2eq), temperature rises to room temperature, reacts 16 hours.With the cancellation of 2mL saturated sodium bicarbonate, ethyl acetate extraction (20mL * 3), anhydrous magnesium sulfate drying filters, column chromatography (sherwood oil: ethyl acetate=40: 1) obtain N-(1-naphthyl ethyl) aniline, yield: 86%, ee:85%.
Embodiment 54: chiral catalyst 21 catalytic asymmetric imines reduction reactions
In the tool plug test tube of 5mL, pack into catalyzer 21 (29.6mg, 0.05mmol), (137.5mg 0.5mmol), adds methylene dichloride 2mL to imines, is chilled to 0 ℃, stirs to add SiHCl down
3(100ul, 2eq), temperature rises to room temperature, reacts 16 hours.With the cancellation of 2mL saturated sodium bicarbonate, ethyl acetate extraction (20mL * 3), anhydrous magnesium sulfate drying filters, column chromatography (sherwood oil: ethyl acetate=40: 1) obtain N-(6-is to methoxyl group-2-naphthyl ethyl) aniline, yield: 82%, ee.80%.
Embodiment 55: chiral catalyst 7 catalytic asymmetric imines reduction reactions
In the tool plug test tube of 5mL, pack into catalyzer 7 (15.5mg, 0.05mmol), (111.5mg 0.5mmol), adds methylene dichloride 2mL to imines, is chilled to 0 ℃, stirs to add SiHCl down
3(100ul, 2eq), temperature rises to room temperature, reacts 16 hours.With the cancellation of 2mL saturated sodium bicarbonate, ethyl acetate extraction (20mL * 3), anhydrous magnesium sulfate drying filters, column chromatography (sherwood oil: ethyl acetate=40: 1) obtain N-(1-phenyl butyl) aniline, yield: 88%, ee:80%.
Claims (13)
1, a kind of optical pure diamide compound, its structural formula is as follows:
Be configured as L or D, wherein: Het represents that the basic framework of this compounds is the 4-8 unit heterocycle of nitrogen atom, R
1, R
2And R
3Be respectively hydrogen, alkyl, replacement alkyl, contain heteroatomic alkyl or substituting group contains heteroatomic alkyl, R
1And R
2Or R
2And R
3Become 3-8 unit ring, X is nitrogen or Sauerstoffatom, and Y is carbonic acyl radical, alkylsulfonyl or phosphoryl, R
4For the alkyl of alkyl, replacement, contain heteroatomic alkyl, substituting group contains heteroatomic alkyl or ZR
4(wherein: Z is nitrogen or Sauerstoffatom).
2, a kind of optical pure diamide compound, its structural formula is as follows:
Be configured as L or D, wherein: Het represents that the basic framework of this compounds is the 4-8 unit saturated heterocyclic of nitrogen atom, R
1And R
2Be respectively alkyl, replacement alkyl, contain heteroatomic alkyl or substituting group contains heteroatomic alkyl, R
1And R
2Become 3-8 unit ring, R
3Be hydrogen atom, X is nitrogen or Sauerstoffatom, and Y is carbonic acyl radical, alkylsulfonyl or phosphoryl, R
4For the alkyl of alkyl, replacement, contain heteroatomic alkyl, substituting group contains heteroatomic alkyl or ZR
4(wherein: Z is nitrogen or Sauerstoffatom).
3, a kind of optical pure diamide compound, its structural formula is as follows:
Be configured as L or D, wherein: Het represents that the basic framework of this compounds is the hexa-atomic saturated heterocyclic of nitrogen atom, R
1And R
2Be phenyl or substituted-phenyl simultaneously, R
3Be hydrogen atom, X is nitrogen or Sauerstoffatom, and Y is a carbonic acyl radical, R
4For the alkyl of alkyl, replacement, contain heteroatomic alkyl, substituting group contains heteroatomic alkyl or ZR
4(wherein: Z is nitrogen or Sauerstoffatom).
4, a kind of optical pure diamide compound, its structural formula is as follows:
Be configured as L or D, wherein: Ph is phenyl or is with substituent phenyl, and X is nitrogen or Sauerstoffatom, R be alkyl, replacement alkyl, contain heteroatomic alkyl or substituting group contains heteroatomic alkyl.
5,, it is characterized in that described alkyl can be alkyl, thiazolinyl, alkynyl or aryl according to the described optical pure diamide compound of one of claim 1-4.
6, optical pure diamide compound according to claim 5 is characterized in that described alkyl is the alkyl that contains the straight or branched of 1 to 24 carbon atom, the alkyl that can be replaced by one or more groups, contains at least one carbon atom on heteroatomic alkyl or the alkyl and contained the alkyl that heteroatoms replaces by what heteroatoms replaced.
7, optical pure diamide compound according to claim 5 is characterized in that described thiazolinyl is the thiazolinyl that contains the straight or branched that contains two keys at least of 1 to 24 carbon atom, the thiazolinyl that can be replaced by one or more groups, contains heteroatomic thiazolinyl or at least one carbon atom and contained the thiazolinyl that heteroatoms replaces by what heteroatoms replaced.
8, optical pure diamide compound according to claim 5 is characterized in that described alkynyl is the alkynyl that contains a triple-linked straight or branched at least that contains 1 to 24 carbon atom, the alkynyl that can be replaced by one or more groups, contains heteroatomic alkynyl or at least one carbon atom and contained the alkynyl that heteroatoms replaces by what heteroatoms replaced.
9, optical pure diamide compound according to claim 5, it is characterized in that described aryl be contain that one or more aromatic rings condense substituting group together, the aromatic base that is connected with each other, the aromatic base that connects by methylene radical, vinyl or the aromatic base that connects together by carbonyl, described aryl contains 1-20 carbon atom, the aryl that can be replaced by one or more groups, contains heteroatomic aryl or at least one carbon atom and is contained aryl, aralkyl, arylalkenyl or the sweet-smelling alkynyl that heteroatoms replaces by what heteroatoms replaced.
10,, it is characterized in that described Het is piperidines or piperazine ring according to the described optical pure diamide compound of one of claim 1-3.
11, optical pure diamide compound according to claim 4 is characterized in that described X is a Sauerstoffatom, and alkyl is a methyl.
12, optical pure diamide compound according to claim 4 is characterized in that and can be undertaken immobilized by Ph, R or other group.
13,, it is characterized in that with the trichlorosilane being reductive agent, stereoselectivity catalysis imines hydrogen transfer reduction according to the application of one of claim 1-12 described optical pure diamide compound.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200510125694 CN1775752A (en) | 2005-12-05 | 2005-12-05 | Optical pure diamide compound and its use |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200510125694 CN1775752A (en) | 2005-12-05 | 2005-12-05 | Optical pure diamide compound and its use |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1775752A true CN1775752A (en) | 2006-05-24 |
Family
ID=36765492
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200510125694 Pending CN1775752A (en) | 2005-12-05 | 2005-12-05 | Optical pure diamide compound and its use |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1775752A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011057430A1 (en) * | 2009-11-13 | 2011-05-19 | 中国科学院成都生物研究所 | Chiral n-sulfinyl amino acid amide compounds, preparation method and use thereof |
| CN103936596A (en) * | 2014-02-13 | 2014-07-23 | 浙江大学 | Method used for catalytic reduction of imine with saccharide-derivatized amino alcohol |
-
2005
- 2005-12-05 CN CN 200510125694 patent/CN1775752A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011057430A1 (en) * | 2009-11-13 | 2011-05-19 | 中国科学院成都生物研究所 | Chiral n-sulfinyl amino acid amide compounds, preparation method and use thereof |
| CN103936596A (en) * | 2014-02-13 | 2014-07-23 | 浙江大学 | Method used for catalytic reduction of imine with saccharide-derivatized amino alcohol |
| CN103936596B (en) * | 2014-02-13 | 2016-02-03 | 浙江大学 | The method of the amino alcohol catalyze imine reduction that sugar is derivative |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1173863A (en) | O -carbamoyl -(D) -phenylalanilol compounds and process for preparing the same | |
| CN101080399A (en) | Process for producing optically active epoxy compound, complex for use in the process, and process for producing the same | |
| CN1106396A (en) | Intermediates useful in the production of aromatic amino-alcohol derivatives having anti-diabetic an21443/o1besity properties | |
| CN1102829A (en) | Synthese of taxol, taxol analogs and their intermediates with variable A-ring side chain structures and compositions thereof | |
| CN1914202A (en) | Process for preparation of 1-(2s,3s)-2-benzhydryl-n-(5-tert-butyl-2-methoxybenzyl)quinuclidin-3-amine | |
| CN1527825A (en) | Method for the preparation of escitalopram | |
| CN1076016C (en) | O-carbamoyl-phenylalaninol compounds, their pharmaceutically useful salts and process for preparing the same | |
| CN101068782A (en) | Process for the synthesis of 4-(3-sulfonylphenyl)-piperidines | |
| Voznesenskaia et al. | Enantioselective synthesis of α-perfluoroalkylated prolines, their 6, 7-membered homologues and derivatives | |
| CN1927830A (en) | Compound of optically pure sulfenamides and application thereof | |
| CN1487941A (en) | Synthesis of temozolomide and analogs | |
| CN1273455C (en) | Process for preparation of 1-1 protected n ring nitrogen containing cyclic polyamines and products thereof | |
| CN1775752A (en) | Optical pure diamide compound and its use | |
| CN1626524A (en) | Dual functions ligand compound of chirality dioxazoline, preparation and application | |
| CN101074207A (en) | Soluble chiral diamino derivative, its production and use | |
| CN1232519C (en) | Method for producing 5-(1piperazinyl)-benzofuran-2-carboxamide by transition metal-catalyzed amination | |
| CN1080259C (en) | Processes for preparing cyclic compounds | |
| CN1446793A (en) | Method for mfg. dien | |
| CN101054355A (en) | Compound of optically pure disulfenamides and application thereof | |
| CN1968941A (en) | Method for producing 3-aminomethyltetrahydrofuran derivative | |
| CN1535962A (en) | Method of preparing olefine oxide | |
| CN1832918A (en) | Process for producing optically active 1-alkyl-substituted 2,2,2-trifluoroethylamine | |
| CN1759100A (en) | New process for preparing 4-aminomethyl-3-alkoxyiminopyrrolidine methanesulfonate | |
| CN1314880A (en) | Novel method for preparing optically active alpha-aminonitriles | |
| CN1930116A (en) | Chiral tertiary aminoalkylnaphthols |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C12 | Rejection of a patent application after its publication | ||
| RJ01 | Rejection of invention patent application after publication |
Open date: 20060524 |