CN103073516A - Derivative containing halogen light active oxazolidinone and preparation method thereof - Google Patents
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- CN103073516A CN103073516A CN2013100025201A CN201310002520A CN103073516A CN 103073516 A CN103073516 A CN 103073516A CN 2013100025201 A CN2013100025201 A CN 2013100025201A CN 201310002520 A CN201310002520 A CN 201310002520A CN 103073516 A CN103073516 A CN 103073516A
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- AXMSEDAJMGFTLR-XRSDMRJBSA-N O=C(c1ccccc1P(c1ccccc1)c1ccccc1)N[C@H](CCCC1)[C@@H]1NC(c1ccccc1P(c1ccccc1)c1ccccc1)=O Chemical compound O=C(c1ccccc1P(c1ccccc1)c1ccccc1)N[C@H](CCCC1)[C@@H]1NC(c1ccccc1P(c1ccccc1)c1ccccc1)=O AXMSEDAJMGFTLR-XRSDMRJBSA-N 0.000 description 1
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- C07D203/04—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D203/06—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
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- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/08—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D263/16—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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Abstract
The invention discloses a derivative containing halogen light active oxazolidinone and a preparation method thereof. The structural formula of the compound is shown as the formula I. N-Bromosuccinimide serves as a bromine source, a complex of chiral phosphine ligand and lewis acid serves as a catalyst, olefin substrates with different catalyzing structures are subjected to asymmetric bromine amine cyclization reaction, and the derivative containing halogen light active oxazolidinone is synthesized and prepared through a simple column chromatography post-processing step. An ee (enantiomer excess) value can achieve highest to 97%. The reaction can be amplified to a gram level, the ee value of products after recrystallization can achieve 99%, and a potential industrial application value is provided. Reaction products can be further derived into various useful compounds, and product application values are achieved.
Description
Technical field
The present invention relates to a kind of Halogen photolytic activity oxazoline ketone derivatives and preparation method thereof.
Background technology
The halogenating reaction of alkene is one of most important elementary reaction in the synthetic chemistry, for the functionalization of alkene provides very simple and effective approach.Asymmetric halogenating reaction to alkene then can be introduced two chirality heteroatomss simultaneously on two keys, multiple conversion can further occur the halogen atom in the product, such as stereoselective substitution reaction etc., thereby becomes important synthon in the organic synthesis.To the asymmetric halogenating reaction of alkene since its great importance caused chemist's broad interest, and obtained greater advance in recent years.At present, the system of Chiral Amine catalysis report is more, lactonizes but mostly be confined to asymmetric halogen.Also have in addition chirality Lewis acid, the catalysis example of the bronsted acid of chirality and chirality palladium.Yet this problem still has a difficult problem that much has challenge not yet to solve at present.Photolytic activity oxazoline ketone derivatives is that a kind of it can be used as the synthon in the organic reaction at the very important compound in organic synthesis field, also can be used as the chiral auxiliary in the asymmetric synthesis.
Summary of the invention
One of purpose of the present invention provides a kind of Halogen photolytic activity oxazoline ketone derivatives.
The Halogen photolytic activity oxazoline ketone derivatives that the present invention synthesized, its structural formula is suc as formula shown in the I:
Among the formula I, R is selected from any one in the following radicals: methyl, phenyl and substituted-phenyl; Neighbour in the described substituted-phenyl,, any one or two positions are replaced by following any one group in the contraposition: methyl, nitro, fluorine atom, chlorine atom and bromine atoms;
R
1Be selected from the following radicals any one: hydrogen, alkyl, contain substituent alkyl and cycloalkyl; Described alkyl can be the straight or branched alkyl of C1-C16; The described substituting group that contains in the substituent alkyl can be in alkyl the optional position replace, described substituting group can be selected from following any one: phenyl, benzyloxy, ether, ester group, sulphonyl ester group, amido, alkynyl, thiazolinyl, cyano group, fluorine atom, chlorine atom, bromine atoms and iodine atom; Described cycloalkyl is the cycloalkyl of C3-C8.
R
2Be selected from hydrogen or alkyl, alkyl can be the alkyl of C1-C5.
Two of purpose of the present invention provides that a kind of substrate is cheap, reaction conditions is gentle, the method for easy and simple to handle, synthetic above-mentioned Halogen photolytic activity oxazoline ketone derivatives with suitability for industrialized production potentiality.
The method for preparing Halogen photolytic activity oxazoline ketone derivatives provided by the present invention comprises the steps:
Under the katalysis of the title complex that chiral phosphine ligand and metal Lewis acid form, olefin substrate shown in bromine source shown in the formula V and the formula II is carried out the bromo-amine cyclization in organic solvent, react the complete compound shown in the formula I that obtains.
In the aforesaid method, among the described formula II, R is selected from any one in the following radicals: methyl, phenyl and substituted-phenyl; Neighbour in the described substituted-phenyl,, any one or two positions are replaced by following any one group in the contraposition: methyl, nitro, fluorine atom, chlorine atom and bromine atoms; R
1Be selected from hydrogen, alkyl, contain substituent alkyl or cycloalkyl, alkyl can be the straight or branched alkyl of C1-C16; Substituting group can in the optional position of alkyl, can be phenyl, benzyloxy, ether, ester group, sulphonyl ester group, amido, alkynyl, thiazolinyl, cyano group, fluorine, chlorine, bromine, iodine atom; Described cycloalkyl is the cycloalkyl of C3-C8; R
2Be selected from hydrogen or alkyl, alkyl can be the alkyl of C1-C5.
Among the described formula V, bromine source preferred formula V-a (the N-bromo-succinimide is called for short NBS).
The configuration of described chiral phosphine ligand can be (R, R) type or (S, S) type, specifically shown in formula III:
Described metal Lewis acid is specifically suc as formula IV institute formula:
M (OTf)
x(formula IV)
In the formula III, Ar is selected from phenyl or substituted-phenyl, the neighbour in the described substituted-phenyl,, any one or two positions are replaced by following any one group in the contraposition: methoxyl group and methyl.
Among the described formula IV, M represents metallic element, and OTf represents the trifluoromethanesulfonic acid root.M (OTf) x is specifically as follows Sc (OTf)
3, Sm (OTf)
3, La (OTf)
3, Y (OTf)
3, Yb (OTf)
3, Cu (OTf)
2, Zn (OTf)
2, Hf (OTf)
3Or Pr (OTf)
3, preferred Sc (OTf)
3
In the aforesaid method, the concentration of olefin substrate shown in the formula II in reaction solution is 0.05～1 mol/L, preferred 0.07-0.1 mol/L.
The molar ratio of olefin substrate is 1～5: 1 shown in bromine source shown in the described formula V and the formula II, preferred 1.2: 1.
Lewis acidic mol ratio shown in chiral ligand shown in the formula III and the formula IV is 0.8～1.5: 1 in the described title complex, preferred 1: 1.The molar ratio of olefin substrate is 0.01～0.2: 1 shown in the title complex that Lewis acid shown in chiral ligand shown in the formula III and the formula IV forms and the formula II, preferred 0.02～0.1: 1.
In the described bromo-amine reactions steps, temperature of reaction is-80 ℃～25 ℃, and preferred-50 ℃ to-30 ℃, the reaction times is 18～72 hours, preferred 48～72 hours.
Described organic solvent is selected from least a in benzene, toluene, trichloromethane, ethylene dichloride and the methylene dichloride, and preferred volume ratio is 3: 1 toluene and the mixed solvent of methylene dichloride.
The present invention can carry out multiple deriving by the Halogen photolytic activity oxazoline ketone derivatives shown in the formula I of asymmetric halogenating reaction acquisition, as being hydrolyzed the very useful photolytic activity aziridine derivative of generation, it all has very important application prospect in fields such as medicine, agricultural, chemical industry.
Specific as follows to the example that the conversion of the Halogen photolytic activity oxazoline ketone derivatives shown in the formula I is derived:
(1) Halogen photolytic activity oxazoline ketone derivatives and the various nucleophilic reagent shown in the formula I reacted in solvent, the bromine atoms replacement is obtained a series of derivatives (shown in VI-VIII).
Among the formula VI-VIII, R, R
1, R
2Definition cotype I.
Described various nucleophilic reagent can be corresponding sodium salt or lithium salts.Described solvent can be DMF, methyl-sulphoxide, tetrahydrofuran (THF) or acetone.
(2) the Halogen photolytic activity oxazoline ketone derivatives shown in formula I or the formula VIII is hydrolyzed under alkaline condition can be converted into corresponding photolytic activity aziridine derivative (shown in IX or XI).
Among formula IX and the XI, R, R
1, R
2Definition cotype I.R among the formula IX
1And R
2Be in trans, R among the formula XI
1And R
2Be in cis.
Described alkali can be salt of wormwood, yellow soda ash, Quilonum Retard, saleratus, sodium bicarbonate, lithium bicarbonate, potassium hydroxide, sodium hydroxide, lithium hydroxide.Described solvent can be methyl alcohol, ethanol, propyl alcohol, Virahol.
(3) the photolytic activity aziridine derivative shown in formula IX or the XI can be converted into corresponding photolytic activity epoxy derivative (shown in X) under the metal hydride condition.
Among the formula X, R, R
1, R
2Definition cotype I.
Described metal hydride can be sodium hydride, potassium hydride KH.Described solvent can be tetrahydrofuran (THF) or ether.
The present invention is take the N-bromo-succinimide as the bromine source, chiral phosphine ligand and lewis acidic title complex are as catalyzer, the olefin substrate of catalysis different structure is carried out asymmetric bromo-amine cyclization, by simple column chromatography post-processing step, synthesizes and has prepared photoactive oxazoline ketone derivatives.Enantiomeric excess value (ee value) is the highest can to reach 97%.This reaction can be amplified to the gram level, and product ee value behind recrystallization can reach 99%, has potential industrial application value.And can further be derivatized to multiple useful compound to reaction product, realize the using value of product.
The Halogen photolytic activity oxazoline ketone derivatives that obtains by asymmetric halogenating reaction among the present invention can be hydrolyzed and generate the photolytic activity aziridine derivative, and can reset further to derive by aza-Payne and obtain the photolytic activity epoxy derivative, these two kinds of compounds not only extensively exist in natural and non-natural bioactive molecules, and be very important organic synthesis intermediate, all have very important application prospect in fields such as medicine, agricultural, chemical industry.
Description of drawings
Fig. 1 is the synthetic route chart of compound formula I-a.
Fig. 2 is for being catalyzed and synthesized the synthetic route chart of compound formula I-a by part formula III-b.
Fig. 3 is the synthetic route chart of compound formula I-b.
Fig. 4 is the synthetic route chart of compound formula I-c.
Fig. 5 is the synthetic route chart of compound formula I-d.
Fig. 6 is the synthetic route chart of compound formula I-e.
Fig. 7 is the synthetic route chart of compound formula I-f.
Fig. 8 is the synthetic route chart of compound formula I-g.
Fig. 9 is the synthetic route chart of compound formula I-h.
Figure 10 is the synthetic route chart of compound formula I-i.
Figure 11 is the synthetic route chart of compound formula I-j.
Figure 12 is the synthetic route chart of compound formula I-k.
Figure 13 is the synthetic route chart of compound formula I-l.
Figure 14 is the synthetic route chart of compound formula I-m.
Figure 15 is the synthetic route chart of compound formula I-n.
Figure 16 is the synthetic route chart of compound formula I-o.
Figure 17 is the synthetic route chart of iodine synthetic compound formula I-a.
Figure 18 is the synthetic route chart of compound formula VI-a.
Figure 19 is the synthetic route chart of compound formula VII-a.
Figure 20 is the synthetic route chart of compound formula VIII-a.
Figure 21 is the synthetic route chart of compound formula IX-a.
Figure 22 is the synthetic route chart of compound formula X-a.
Figure 23 is the synthetic route chart of compound formula XI-a.
Embodiment
Below by specific embodiment method of the present invention is described, but the present invention is not limited thereto.
Experimental technique described in the following embodiment if no special instructions, is ordinary method; Described reagent and material if no special instructions, all can obtain from commercial channels.
Institute's formula olefin substrate all can room temperature reaction obtains in methylene dichloride with corresponding sulfonyl isocyanate (as: methylsulfonyl isocyanic ester, tolylsulfonyl isocyanic ester etc.) by the corresponding vinyl carbinol that is easy to get among the formula II.Reference is as follows: Friesen, R.W.; Kolaczewska, A.E.J.Org.Chem.1991,56,4888.
Formula II-a, b, c, the corresponding vinyl carbinol of n can obtain from commercial channels.
Formula II-d, e, the corresponding vinyl carbinol of i can prepare by following literature method: Chatterjee, I.;
R.; Studer, A.Angew.Chem., Int.Ed.2011,50,11257.
The corresponding vinyl carbinol of formula II-f can prepare by following literature method: Schomaker, J.M.; Pulgam, V.R.; Borhan, B.J.Am.Chem.Soc.2004,126,13600.
The corresponding vinyl carbinol of formula II-l can prepare by following literature method:
A.; Shi, L.; Otte, M.J.Am.Chem.Soc.2010,132,11858.
The corresponding vinyl carbinol of formula II-h takes off MOM protection preparation by (Z)-6-Methyloxymethyloxy-4-hexen-1-ol again by hydroxyl being carried out the Ts protection.Reference is as follows: Hirai, Y.; Watanabe, J.; Nozaki, T.; Yokoyama, H.; Yamaguchi, S.J.Org.Chem.1997,62,776.
The corresponding vinyl carbinol of formula II-j is prepared by replacing OTs by chlorine by the corresponding vinyl carbinol of formula II-h.Reference is as follows: Kumar, P.; Upadhyay, R.K.; Pandey, R.K.Tetrahedron:Asymmetry 2004,15, and 3955.
The corresponding vinyl carbinol of formula II-k is prepared by following literature method by the corresponding vinyl carbinol of formula II-h: Chandrasekhar, S.; Reddy, N.R.; Rao, Y.S.Tetrahedron 2006,62, and 12098.
The corresponding vinyl carbinol of formula II-m is prepared by following literature method by (Z)-6-Methyloxymethyloxy-4-hexen-1-ol: Hirai, Y.; Watanabe, J.; Nozaki, T.; Yokoyama, H.; Yamaguchi, S.J.Org.Chem.1997,62,776.
The corresponding vinyl carbinol of formula II-o can prepare by following literature method: Sreekumar, C.; Darst, K.P.; Still, W.C.J.Org.Chem.1980,45,4260.
Part shown in the formula III can obtain from commercial channels, also can prepare Trost by following literature method, B.M.; VanVranken, D.L.; Bingel, C.J.Am.Chem.Soc.1992,114,9327.
Embodiment 1, synthetic compound formula I-a (seeing structural formula I-a)
Ts represents p-toluenesulfonyl in the following formula.
In reaction tube, be weighed into part (shown in formula III-a) (0.00691g, 0.01mmol) and Sc (OTf)
3(0.00492g, 0.01mmol), the mixed solvent of adding PhMe/DCM=3/1 (v/v, 4.0mL) stirs 0.5h in 0 ℃.Add NBS (0.1068g, 0.60mmol), behind 0 ℃ of stirring 5min, be chilled to-50 ℃, add again olefin substrate (shown in the formula II-a) (0.1415g, 0.5mmol) the solution of PhMe/DCM=3/1 (v/v, 1.0mL), in-50 ℃ of reaction 48h.After finishing, reaction adds triethylamine (0.5mL) cancellation reaction, (eluent is sherwood oil: ethyl acetate=5/1 directly to be spin-dried for rear column chromatography, v/v), get 0.1589g white solid oxazoline ketone product (shown in the formula I-a), productive rate 88%, enantiomeric excess 96% (HPLC mensuration).
The HPLC condition: chirality AD-H post, moving phase: the volume ratio of normal hexane and Virahol is 85: 15 mixed solvent, flow velocity: 1.0mL/min, absorbing wavelength: 230nm.
The structural identification result is as follows:
1H NMR (400MHz, CDCl
3) δ 7.94 (d, J=8.4Hz, 2H), 7.37 (d, J=8.4Hz, 2H), 4.87-4.81 (m, 1H), (4.48-4.40 m, 2H), 4.37 (dd, J=9.2,8.8Hz, 1H), 2.46 (s, 3H), (1.78-1.66 m, 1H), 1.62-1.48 (m, 1H), (1.03 t, J=7.2Hz, 3H);
13C NMR (100MHz, CDCl
3) δ 152.2,146.3,134.6,130.1,128.6,65.1,60.3,56.0,23.2,21.9,12.3.
This product determines that through monocrystalline absolute configuration is (R, R).
Embodiment 2, by part formula III-b synthetic compound formula I-a (seeing structural formula I-a)
Ts represents p-toluenesulfonyl in the following formula.
In reaction tube, be weighed into part (shown in formula III-b) (0.00788g, 0.01mmol) and Sc (OTf)
3(0.00492g, 0.01mmol), the mixed solvent of adding PhMe/DCM=3/1 (v/v, 4.0mL) stirs 0.5h in 25 ℃.Add NBS (0.1068g, 0.60mmol), behind 25 ℃ of stirring 5min, be chilled to-50 ℃, add again olefin substrate (shown in the formula II-a) (0.1415g, 0.5mmol) the solution of PhMe/DCM=3/1 (v/v, 1.0mL), in-50 ℃ of reaction 48h.After finishing, reaction adds triethylamine (0.5mL) cancellation reaction, (eluent is sherwood oil: ethyl acetate=5/1 directly to be spin-dried for rear column chromatography, v/v), get 0.1532g white solid oxazoline ketone product (shown in the formula I-a), productive rate 85%, enantiomeric excess 97% (HPLC mensuration).
The HPLC condition: chirality AD-H post, moving phase: the volume ratio of normal hexane and Virahol is 85: 15 mixed solvent, flow velocity: 1.0mL/min, absorbing wavelength: 230nm.
The structural identification result is as follows:
1H NMR (400MHz, CDCl
3) δ 7.94 (d, J=8.4Hz, 2H), 7.37 (d, J=8.4Hz, 2H), 4.87-4.81 (m, 1H), (4.48-4.40 m, 2H), 4.37 (dd, J=9.2,8.8Hz, 1H), 2.46 (s, 3H), (1.78-1.66 m, 1H), 1.62-1.48 (m, 1H), (1.03 t, J=7.2Hz, 3H);
13C NMR (100MHz, CDCl
3) δ 152.2,146.3,134.6,130.1,128.6,65.1,60.3,56.0,23.2,21.9,12.3.
Embodiment 3, synthetic compound formula I-b (seeing structural formula I-b)
Ts represents p-toluenesulfonyl in the following formula.
In reaction tube, be weighed into part (shown in formula III-a) (0.00691g, 0.01mmol) and Sc (OTf)
3(0.00492g, 0.01mmol), the mixed solvent of adding PhMe/DCM=3/1 (v/v, 4.0mL) stirs 0.5h in 0 ℃.Add NBS (0.1068g, 0.60mmol), behind 0 ℃ of stirring 5min, be chilled to-50 ℃, add again olefin substrate (shown in the formula II-b) (0.1345g, 0.5mmol) the solution of PhMe/DCM=3/1 (v/v, 1.0mL), in-50 ℃ of reaction 72h.After finishing, reaction adds triethylamine (0.5mL) cancellation reaction, (eluent is sherwood oil: ethyl acetate=5/1 directly to be spin-dried for rear column chromatography, v/v), get 0.1381g white solid oxazoline ketone product (shown in the formula I-b), productive rate 79%, enantiomeric excess 96% (HPLC mensuration).
The HPLC condition: chirality AD-H post, moving phase: the volume ratio of normal hexane and Virahol is 85: 15 mixed solvent, flow velocity: 1.0mL/min, absorbing wavelength: 230nm.
The structural identification result is as follows:
1H NMR (400MHz, CDCl
3) δ 7.95 (d, J=8.4Hz, 2H), 7.37 (d, J=8.4Hz, 2H), 4.84-4.75 (m, 1H), (4.74-4.64 m, 1H), 4.44 (dd, J=10.0,3.6Hz, 1H), 4.36 (t, J=9.2Hz, 1H), 2.45 (s, 3H), (1.55 d, J=6.8Hz, 3H);
13C NMR (100MHz, CDCl
3) δ 152.1,146.3,134.5,130.2,128.6,64.6,60.2,46.2,21.9,17.2.
Embodiment 4. synthetic compound formula I-c (seeing structural formula I-c)
Ts represents p-toluenesulfonyl in the following formula.
In reaction tube, be weighed into part (shown in formula III-a) (0.00691g, 0.01mmol) and Sc (OTf)
3(0.00492g, 0.01mmol), the mixed solvent of adding PhMe/DCM=3/1 (v/v, 4.0mL) stirs 0.5h in 0 ℃.Add NBS (0.1068g, 0.60mmol), behind 0 ℃ of stirring 5min, be chilled to-50 ℃, add again olefin substrate (shown in the formula II-c) (0.1695g, 0.5mmol) the solution of PhMe/DCM=3/1 (v/v, 1.0mL), in-50 ℃ of reaction 48h.After finishing, reaction adds triethylamine (0.5mL) cancellation reaction, (eluent is sherwood oil: ethyl acetate=5/1 directly to be spin-dried for rear column chromatography, v/v), get 0.1886g colourless liquid oxazoline ketone product (shown in the formula I-c), productive rate 90%, enantiomeric excess 96% (HPLC mensuration).
The HPLC condition: chirality AD-H post, moving phase: the volume ratio of normal hexane and Virahol is 85: 15 mixed solvent, flow velocity: 1.0mL/min, absorbing wavelength: 230nm.
The structural identification result is as follows:
1H NMR (400MHz, CDCl
3) δ 7.96 (d, J=8.4Hz, 2H), 7.37 (d, J=8.4Hz, 2H), 4.88-4.80 (m, 1H), (4.52-4.42 m, 2H), 4.38 (dd, J=9.2,8.8Hz, 1H), 2.46 (s, 3H), (1.68-1.47 m, 3H), 1.33-1.11 (m, 7H), (0.88 t, J=7.2Hz, 3H);
13C NMR (100MHz, CDCl
3) δ 152.2,146.3,134.8,130.2,128.6,65.1,60.3,54.0,31.7,29.6,28.6,27.7,22.7,21.9,14.2.
Embodiment 5. synthetic compound formula I-d (seeing structural formula I-d)
Ts represents p-toluenesulfonyl in the following formula.
In reaction tube, be weighed into part (shown in formula III-a) (0.00691g, 0.01mmol) and Sc (OTf)
3(0.00492g, 0.01mmol), the mixed solvent of adding PhMe/DCM=3/1 (v/v, 4.0mL) stirs 0.5h in 0 ℃.Add NBS (0.1068g, 0.60mmol), behind 0 ℃ of stirring 5min, be chilled to-50 ℃, add again olefin substrate (shown in the formula II-d) (0.1797g, 0.5mmol) the solution of PhMe/DCM=3/1 (v/v, 1.0mL), in-50 ℃ of reaction 48h.After finishing, reaction adds triethylamine (0.5mL) cancellation reaction, (eluent is sherwood oil: ethyl acetate=5/1 directly to be spin-dried for rear column chromatography, v/v), get 0.1817g white solid oxazoline ketone product (shown in the formula I-d), productive rate 83%, enantiomeric excess 93% (HPLC mensuration).
The HPLC condition: chirality AD-H post, moving phase: the volume ratio of normal hexane and Virahol is 85: 15 mixed solvent, flow velocity: 1.0mL/min, absorbing wavelength: 230nm.
The structural identification result is as follows:
1H NMR (400MHz, CDCl
3) δ 7.89 (d, J=8.4Hz, 2H), 7.35 (d, J=8.4Hz, 2H), 7.32-7.26 (m, 2H), 7.25-7.19 (m, 1H), (7.07 d, J=7.2Hz, 2H), 4.90-4.82 (m, 1H), (4.54-4.43 m, 2H), 4.39 (dd, J=9.6,8.8Hz, 1H), 3.05-2.91 (m, 1H), 2.63-2.50 (m, 1H), (2.45 s, 3H), 2.00-1.78 (m, 2H);
13C NMR (100MHz, CDCl
3) δ 152.2,146.3,139.8,134.7,130.2,128.8,128.65,128.57,126.7,65.2,60.1,53.3,33.6,31.5,21.9.
Embodiment 6. synthetic compound formula I-e (seeing structural formula I-e)
Ts represents p-toluenesulfonyl in the following formula.
In reaction tube, be weighed into part (shown in formula III-a) (0.01727g, 0.025mmol) and Sc (OTf) 3 (0.01230g, 0.025mmol), add PhMe/DCM=3/1 (v/v, 4.0mL) mixed solvent, stir 0.5h in 0 ℃.Add NBS (0.1068g, 0.60mmol), behind 0 ℃ of stirring 5min, be chilled to 50 ℃, add again olefin substrate (shown in the formula II-e) (0.1687g, 0.5mmol) the solution of PhMe/DCM=3/1 (v/v, 1.0mL), in-50 ℃ of reaction 72h.After finishing, reaction adds triethylamine (0.5mL) cancellation reaction, (eluent is sherwood oil: ethyl acetate=5/1 directly to be spin-dried for rear column chromatography, v/v), get 0.1473g white solid oxazoline ketone product (shown in the formula I-e), productive rate 71%, enantiomeric excess 96% (HPLC mensuration).
The HPLC condition: chirality AD-H post, moving phase: the volume ratio of normal hexane and Virahol is 85: 15 mixed solvent, flow velocity: 1.0mL/min, absorbing wavelength: 230nm.
The structural identification result is as follows:
1H NMR (400MHz, CDCl
3) δ 7.96 (d, J=8.4Hz, 2H), 7.38 (d, J=8.4Hz, 2H), (4.90-4.79 m, 1H), 4.54 (dd, J=9.6,3.2Hz, 1H), 4.40 (t, J=4.0Hz, 1H), 4.34 (t, J=9.6,9.2Hz, 1H), 2.46 (s, 3H), (1.75-1.65 m, 3H), 1.64-1.54 (m, 1H), 1.52-1.40 (m, 2H), 1.38-1.20 (m, 2H), 1.20-1.02 (m, 3H);
13C NMR (100MHz, CDCl
3) δ 152.4,146.2,134.8,130.1,128.5,66.2,61.3,59.8,38.3,32.8,29.4,26.1,25.9,25.8,21.9.
Embodiment 7. synthetic compound formula I-f (seeing structural formula I-f)
Ts represents p-toluenesulfonyl in the following formula, and Bn represents benzyl.
In reaction tube, be weighed into part (shown in formula III-a) (0.01727g, 0.025mmol) and Sc (OTf) 3 (0.01230g, 0.025mmol), add PhMe/DCM=3/1 (v/v, 4.0mL) mixed solvent, stir 0.5h in 0 ℃.Add NBS (0.1068g, 0.60mmol), behind 0 ℃ of stirring 5min, be chilled to-50 ℃, add again olefin substrate (shown in the formula II-f) (0.1875g, 0.5mmol) the solution of PhMe/DCM=3/1 (v/v, 1.0mL), in-50 ℃ of reaction 72h.After finishing, reaction adds triethylamine (0.5mL) cancellation reaction, (eluent is sherwood oil: ethyl acetate=5/1 directly to be spin-dried for rear column chromatography, v/v), get 0.1820g white solid oxazoline ketone product (shown in the formula I-f), productive rate 80%, enantiomeric excess 94% (HPLC mensuration).
The HPLC condition: chirality AD-H post, moving phase: the volume ratio of normal hexane and Virahol is 85: 15 mixed solvent, flow velocity: 1.0mL/min, absorbing wavelength: 230nm.
The structural identification result is as follows:
1H NMR (400MHz, CDCl
3) δ 7.93 (d, J=8.4Hz, 2H), 7.42-7.28 (m, 5H), (7.28-7.20 m, 2H), 4.88-4.77 (m, 1H), 4.74-4.60 (m, 2H), 4.42 (s, 2H), 4.30 (dd, J=9.2,8.8Hz, 1H), 3.84 (dd, J=11.2,4.4Hz, 1H), 3.71 (dd, J=11.2,5.2Hz, 1H), 2.43 (s, 3H);
13C NMR (100MHz, CDCl
3) δ 152.3,146.1,137.1,134.6,130.0,128.7,128.6,128.1,128.0,73.9,69.3,65.7,58.8,49.1,21.9.
Embodiment 8. synthetic compound formula I-g (seeing structural formula I-g)
Ts represents p-toluenesulfonyl in the following formula, and Ac represents ethanoyl.
In reaction tube, be weighed into part (shown in formula III-a) (0.00691g, 0.01mmol) and Sc (OTf) 3 (0.00492g, 0.01mmol), add PhMe/DCM=3/1 (v/v, 4.0mL) mixed solvent, stir 0.5h in 0 ℃.Add NBS (0.1068g, 0.60mmol), behind 0 ℃ of stirring 5min, be chilled to 50 ℃, add again olefin substrate (shown in the formula II-g) (0.1775g, 0.5mmol) the solution of PhMe/DCM=3/1 (v/v, 1.0mL), in-50 ℃ of reaction 48h.After finishing, reaction adds triethylamine (0.5mL) cancellation reaction, (eluent is sherwood oil: ethyl acetate=5/1 directly to be spin-dried for rear column chromatography, v/v), get 0.1738g white solid oxazoline ketone product (shown in the formula I-g), productive rate 80%, enantiomeric excess 97% (HPLC mensuration).
The HPLC condition: chirality AD-H post, moving phase: the volume ratio of normal hexane and Virahol is 80: 20 mixed solvent, flow velocity: 1.0mL/min, absorbing wavelength: 230nm.
The structural identification result is as follows:
1H NMR (400MHz, CDCl
3) δ 7.95 (d, J=7.6Hz, 2H), 7.38 (d, J=7.6Hz, 2H), 4.89-4.78 (m, 1H), 4.61-4.51 (m, 1H), (4.45 dd, J=9.6,2.8Hz, 1H), 4.38 (t, J=9.2Hz, 1H), 4.00 (t, J=5.6Hz, 2H), (2.46 s, 3H), 2.04 (s, 3H), 2.09-1.94 (m, 1H), 1.89-1.75 (m, 1H), 1.71-1.57 (m, 2H);
13C NMR (100MHz, CDCl
3) δ 171.2,152.1,146.5,134.5,130.2,128.6,65.0,63.2,60.2,53.2,26.8,26.5,21.9,21.1.
Embodiment 9. synthetic compound formula I-h (seeing structural formula I-h)
Ts represents p-toluenesulfonyl in the following formula, and Ph represents phenyl.
In reaction tube, be weighed into part (shown in formula III-a) (0.00691g, 0.01mmol) and Sc (OTf)
3(0.00492g, 0.01mmol), the mixed solvent of adding PhMe/DCM=3/1 (v/v, 4.0mL) stirs 0.5h in 0 ℃.Add NBS (0.1068g, 0.60mmol), behind 0 ℃ of stirring 5min, be chilled to-50 ℃, add again olefin substrate (shown in the formula II-h) (0.2338g, 0.5mmol) the solution of PhMe/DCM=3/1 (v/v, 1.0mL), in-50 ℃ of reaction 48h.After finishing, reaction adds triethylamine (0.5mL) cancellation reaction, (eluent is sherwood oil: ethyl acetate=5/1 directly to be spin-dried for rear column chromatography, v/v), get 0.2048g white solid oxazoline ketone product (shown in the formula I-h), productive rate 75%, enantiomeric excess 97% (HPLC mensuration).
The HPLC condition: chirality AD-H post, moving phase: the volume ratio of normal hexane and Virahol is 80: 20 mixed solvent, flow velocity: 1.0mL/min, absorbing wavelength: 230nm.
The structural identification result is as follows:
1H NMR (400MHz, CDCl
3) δ 7.92 (d, J=8.0Hz, 2H), 7.69 (d, J=8.0Hz, 2H), 7.38 (d, J=8.0Hz, 2H), 7.34 (d, J=8.0Hz, 2H), 4.85-4.74 (m, 1H), 4.47-4.26 (m, 3H), 4.00-3.86 (m, 2H), 2.45 (s, 3H), (2.44 s, 3H), 2.08-1.92 (m, 1H), (1.65-1.51 m, 2H), 1.51-1.38 (m, 1H);
13C NMR (100MHz, CDCl
3) δ 152.0,146.7,145.2,134.3,132.7,130.3,130.2,128.4,128.0,69.2,64.9,59.8,52.8,27.4,26.2,21.9,21.8.
Embodiment 10. synthetic compound formula I-i (seeing structural formula I-i)
Ts represents p-toluenesulfonyl in the following formula, and Ph represents phenyl, and CN represents itrile group.
In reaction tube, be weighed into part (shown in formula III-a) (0.00691g, 0.01mmol) and Sc (OTf) 3 (0.00492g, 0.01mmol), add PhMe/DCM=3/1 (v/v, 4.0mL) mixed solvent, stir 0.5h in 0 ℃.Add NBS (0.1068g, 0.60mmol), behind 0 ℃ of stirring 5min, be chilled to-50 ℃, add again olefin substrate (shown in the formula II-i) (0.1610g, 0.5mmol) the solution of PhMe/DCM=3/1 (v/v, 1.0mL), in-50 ℃ of reaction 48h.After finishing, reaction adds triethylamine (0.5mL) cancellation reaction, (eluent is sherwood oil: ethyl acetate=5/1 directly to be spin-dried for rear column chromatography, v/v), get 0.1503g white solid oxazoline ketone product (shown in the formula I-i), productive rate 75%, enantiomeric excess 96% (HPLC mensuration).
The HPLC condition: chirality AD-H post, moving phase: the volume ratio of normal hexane and Virahol is 80: 20 mixed solvent, flow velocity: 1.0mL/min, absorbing wavelength: 230nm.
The structural identification result is as follows:
1H NMR (400MHz, CDCl
3) δ 7.94 (d, J=7.6Hz, 2H), 7.39 (d, J=7.6Hz, 2H), 4.88-4.76 (m, 1H), (4.56-4.46 m, 1H), 4.46-4.34 (m, 2H), 2.46 (s, 3H), (2.42-2.24 m, 2H), 2.14-2.00 (m, 1H), 1.90-1.57 (m, 3H);
13C NMR (100MHz, CDCl
3) δ 152.0,146.7,134.2,130.3,128.6,118.9,64.9,60.0,52.2,29.0,24.0,21.9,16.7.
Embodiment 11. synthetic compound formula I-j (seeing structural formula I-j)
Ts represents p-toluenesulfonyl in the following formula, and Ph represents phenyl.
In reaction tube, be weighed into part (shown in formula III-a) (0.00691g, 0.01mmol) and Sc (OTf)
3(0.00492g, 0.01mmol), the mixed solvent of adding PhMe/DCM=3/1 (v/v, 4.0mL) stirs 0.5h in 0 ℃.Add NBS (0.1068g, 0.60mmol), behind 0 ℃ of stirring 5min, be chilled to-50 ℃, add again olefin substrate (shown in the formula II-j) (0.1659g, 0.5mmol) the solution of PhMe/DCM=3/1 (v/v, 1.0mL), in 50 ℃ of reaction 48h.After finishing, reaction adds triethylamine (0.5mL) cancellation reaction, (eluent is sherwood oil: ethyl acetate=5/1 directly to be spin-dried for rear column chromatography, v/v), get 0.1796g white solid oxazoline ketone product (shown in the formula I-j), productive rate 87%, enantiomeric excess 96% (HPLC mensuration).
The HPLC condition: chirality AD-H post, moving phase: the volume ratio of normal hexane and Virahol is 85: 15 mixed solvent, flow velocity: 1.0mL/min, absorbing wavelength: 230nm.
The structural identification result is as follows:
1H NMR (400MHz, CDCl
3) δ 7.95 (d, J=8.0Hz, 2H), 7.38 (d, J=8.0Hz, 2H), (4.91-4.80 m, 1H), 4.56-4.35 (m, 3H), 3.51-3.41 (m, 2H), (2.46 s, 3H), 2.22-2.06 (m, 1H), 1.90-1.62 (m, 3H);
13C NMR (100MHz, CDCl
3) δ 152.1,146.5,134.5,130.3,128.6,65.0,60.1,52.8,43.8,30.9,27.4,22.0.
Embodiment 12. synthetic compound formula I-k (seeing structural formula I-k)
Ts represents p-toluenesulfonyl in the following formula, and Ph represents phenyl, and Boc represents tertbutyloxycarbonyl.
In reaction tube, be weighed into part (shown in formula III-a) (0.00691g, 0.01mmol) and Sc (OTf)
3(0.00492g, 0.01mmol), the mixed solvent of adding PhMe/DCM=3/1 (v/v, 4.0mL) stirs 0.5h in 0 ℃.Add NBS (0.1068g, 0.60mmol), behind 0 ℃ of stirring 5min, be chilled to-50 ℃, add again olefin substrate (shown in the formula II-k) (0.2063g, 0.5mmol) the solution of PhMe/DCM=3/1 (v/v, 1.0mL), in-50 ℃ of reaction 48h.After finishing, reaction adds triethylamine (0.5mL) cancellation reaction, (eluent is sherwood oil: ethyl acetate=5/1 directly to be spin-dried for rear column chromatography, v/v), get 0.1232g white solid oxazoline ketone product (shown in the formula I-k), productive rate 50%, enantiomeric excess 92% (HPLC mensuration).
The HPLC condition: chirality AD-H post, moving phase: the volume ratio of normal hexane and Virahol is 85: 15 mixed solvent, flow velocity: 1.0mL/min, absorbing wavelength: 230nm.
The structural identification result is as follows:
1H NMR (400MHz, CDCl
3) δ 7.95 (d, J=7.6Hz, 2H), 7.40 (d, J=7.6Hz, 2H), 4.85-4.78 (m, 1H), 4.58-4.47 (m, 2H), (4.47-4.41 m, 1H), 4.38 (t, J=9.2Hz, 1H), 3.19-3.05 (m, 1H), 3.05-2.93 (m, 1H), (2.47 s, 3H), 1.93-1.78 (m, 1H), 1.76-1.65 (m, 1H), (1.65-1.53 m, 1H), 1.52-1.36 (m, 1H), 1.45 (s, 9H);
13C NMR (100MHz, CDCl
3) δ 156.0,152.1,146.4,134.4,130.2,128.5,79.4,65.0,60.1,53.3,39.6,28.5,28.2,27.0,21.9.
Embodiment 13. synthetic compound formula I-l (seeing structural formula I-l)
Ts represents p-toluenesulfonyl in the following formula, and Ph represents phenyl.
In reaction tube, be weighed into part (shown in formula III-a) (0.01727g, 0.025mmol) and Sc (OTf)
3(0.01230g, 0.025mmol), the mixed solvent of adding PhMe/DCM=3/1 (v/v, 4.0mL) stirs 0.5h in 0 ℃.Add NBS (0.1068g, 0.60mmol), behind 0 ℃ of stirring 5min, be chilled to-50 ℃, add again olefin substrate (shown in the formula II-l) (0.1535g, 0.5mmol) the solution of PhMe/DCM=3/1 (v/v, 1.0mL), in-50 ℃ of reaction 72h.After finishing, reaction adds triethylamine (0.5mL) cancellation reaction, (eluent is sherwood oil: ethyl acetate=5/1 directly to be spin-dried for rear column chromatography, v/v), get 0.1572g white solid oxazoline ketone product (shown in the formula I-l), productive rate 81%, enantiomeric excess 94% (HPLC mensuration).
The HPLC condition: chirality AD-H post, moving phase: the volume ratio of normal hexane and Virahol is 85: 15 mixed solvent, flow velocity: 1.0mL/min, absorbing wavelength: 230nm.
The structural identification result is as follows:
1H NMR (400MHz, CDCl
3) δ 7.98 (d, J=8.0Hz, 2H), 7.38 (d, J=8.0Hz, 2H), 4.98-4.86 (m, 1H), (4.80-4.69 m, 1H), 4.50-4.36 (m, 2H), (2.57-2.43 m, 1H), 2.46 (s, 3H), (2.43-2.29 m, 1H), 2.08 (s, 1H), (1.95-1.81 m, 1H), 1.80-1.66 (m, 1H);
13C NMR (100MHz, CDCl
3) δ 152.1,146.3,134.2,130.2,128.7,81.4,70.5,65.2,59.6,52.2,28.4,21.9,16.8.
Embodiment 14. synthetic compound formula I-m (seeing structural formula I-m)
Ts represents p-toluenesulfonyl in the following formula, and Ph represents phenyl, and Et represents ethyl.
In reaction tube, be weighed into part (shown in formula III-a) (0.00691g, 0.01mmol) and Sc (OTf)
3(0.00492g, 0.01mmol), the mixed solvent of adding PhMe/DCM=3/1 (v/v, 4.0mL) stirs 0.5h in 0 ℃.Add NBS (0.1068g, 0.60mmol), behind 0 ℃ of stirring 5min, be chilled to-50 ℃, add again olefin substrate (shown in the formula II-m) (0.1905g, 0.5mmol) the solution of PhMe/DCM=3/1 (v/v, 1.0mL), in-50 ℃ of reaction 72h.After finishing, reaction adds triethylamine (0.5mL) cancellation reaction, (eluent is sherwood oil: ethyl acetate=5/1 directly to be spin-dried for rear column chromatography, v/v), get 0.1980g colourless liquid oxazoline ketone product (shown in the formula I-m), productive rate 86%, enantiomeric excess 95% (HPLC mensuration).
The HPLC condition: chirality AD-H post, moving phase: the volume ratio of normal hexane and Virahol is 85: 15 mixed solvent, flow velocity: 1.0mL/min, absorbing wavelength: 230nm.
The structural identification result is as follows:
1H NMR (400MHz, CDCl
3) δ 7.94 (d, J=8.0Hz, 2H), 7.39 (d, J=8.0Hz, 2H), 6.81-6.65 (m, 1H), 5.80 (d, J=15.6Hz, 1H), 4.94-4.78 (m, 1H), 4.50-4.36 (m, 3H), (4.19 q, J=6.8Hz, 2H), 2.58-2.41 (m, 1H), (2.45 s, 3H), 2.25-2.10 (m, 1H), 1.76-1.59 (m, 2H), 1.29 (t, J=6.8Hz, 3H);
13C NMR (100MHz, CDCl
3) δ 166.2,152.0,146.5,145.6,134.5,130.2,128.6,123.4,65.0,60.6,60.0,52.6,30.0,28.1,21.9,14.4.
Embodiment 15. synthetic compound formula I-n (seeing structural formula I-n)
Ts represents p-toluenesulfonyl in the following formula, and Ph represents phenyl.
In reaction tube, be weighed into part (shown in formula III-a) (0.01727g, 0.025mmol) and Sc (OTf)
3(0.01230g, 0.025mmol), the mixed solvent of adding PhMe/DCM=3/1 (v/v, 4.0mL) stirs 0.5h in 0 ℃.Add NBS (0.1068g, 0.60mmol), behind 0 ℃ of stirring 5min, be chilled to-50 ℃, add again olefin substrate (shown in the formula II-n) (0.1276g, 0.5mmol) the solution of PhMe/DCM=3/1 (v/v, 1.0mL), in-50 ℃ of reaction 48h.After finishing, reaction adds triethylamine (0.5mL) cancellation reaction, (eluent is sherwood oil: ethyl acetate=5/1 directly to be spin-dried for rear column chromatography, v/v), get 0.1449g weak yellow liquid oxazoline ketone product (shown in the formula I-n), productive rate 87%, enantiomeric excess 89% (HPLC mensuration).
The HPLC condition: chirality AD-H post, moving phase: the volume ratio of normal hexane and Virahol is 80: 20 mixed solvent, flow velocity: 1.0mL/min, absorbing wavelength: 230nm.
The structural identification result is as follows:
1H NMR (400MHz, CDCl
3) δ 7.95 (d, J=8.0Hz, 2H), 7.36 (d, J=8.0Hz, 2H), (4.76-4.68 m, 1H), 4.43 (dd, J=9.2,8.8Hz, 1H), (4.29-4.23 m, 1H), 3.79-3.68 (m, 2H), 2.45 (s, 3H);
13C NMR (100MHz, CDCl
3) δ 151.9,146.2,134.5,130.0,128.7,67.1,56.3,33.4,21.9.
Embodiment 16. synthetic compound formula I-o (seeing structural formula I-o)
Ts represents p-toluenesulfonyl in the following formula, and Ph represents phenyl.
In reaction tube, be weighed into part (shown in formula III-a) (0.00691g, 0.01mmol) and Sc (OTf)
3(0.00492g, 0.01mmol), the mixed solvent of adding PhMe/DCM=3/1 (v/v, 4.0mL) stirs 0.5h in 0 ℃.Add NBS (0.1068g, 0.60mmol), behind 0 ℃ of stirring 5min, be chilled to-50 ℃, add again olefin substrate (shown in the formula II-o) (0.1625g, 0.5mmol) the solution of PhMe/DCM=3/1 (v/v, 1.0mL), in-50 ℃ of reaction 72h.After finishing, reaction adds triethylamine (0.5mL) cancellation reaction, (eluent is sherwood oil: ethyl acetate=5/1 directly to be spin-dried for rear column chromatography, v/v), get 0.1673g weak yellow liquid oxazoline ketone product (shown in the formula I-o), productive rate 83%, enantiomeric excess 91% (HPLC mensuration).
The HPLC condition: chirality AD-H post, moving phase: the volume ratio of normal hexane and Virahol is 85: 15 mixed solvent, flow velocity: 1.0mL/min, absorbing wavelength: 230nm.
The structural identification result is as follows:
1H NMR (400MHz, CDCl
3) δ 7.95 (d, J=8.0Hz, 2H), 7.34 (d, J=8.0Hz, 2H), 4.62 (d, J=12.0Hz, 1H), 4.53 (d, J=9.6Hz, 1H), 3.92 (d, J=9.6Hz, 1H), (2.43 s, 3H), 2.09-1.97 (m, 1H), 1.91 (s, 3H), 1.76-1.56 (m, 2H), 1.47-1.22 (m, 3H), 0.92 (d, J=7.2Hz, 3H);
13C NMR (100MHz, CDCl
3) δ 152.4,146.0,135.0,129.8,129.1,71.4,68.4,60.8,31.9,30.0,26.2,21.9,21.8,14.0.
Embodiment 17, iodine synthetic compound formula I-a (seeing structural formula I-a)
Ts represents p-toluenesulfonyl in the following formula, and Ph represents phenyl.
In reaction flask, be weighed into part (shown in formula III-a) (0.2072g, 0.30mmol) and Sc (OTf)
3(0.1476g, 0.30mmol), the mixed solvent of adding PhMe/DCM=3/1 (v/v, 120.0mL) stirs 0.5h in 0 ℃.Add NBS (3.204g, 18.0mmol), behind 0 ℃ of stirring 5min, be chilled to-50 ℃, add again olefin substrate (shown in the formula II-a) (4.245g, 15.0mmol) the solution of PhMe/DCM=3/1 (v/v, 30.0mL), in-50 ℃ of reaction 48h.After finishing, reaction adds triethylamine (9mL) cancellation reaction, (eluent is sherwood oil: ethyl acetate: methylene dichloride=5/1/3 v/v/v), gets 4.9449g white solid oxazoline ketone product (shown in the formula I-a) directly to be spin-dried for rear column chromatography, productive rate 91%, enantiomeric excess 94%.Product gets 4.4334g white solid oxazoline ketone product (shown in the formula I-a), productive rate 82%, enantiomeric excess＞99% with methylene dichloride/Virahol recrystallization.
The HPLC condition: chirality AD-H post, moving phase: the volume ratio of normal hexane and Virahol is 85: 15 mixed solvent, flow velocity: 1.0mL/min, absorbing wavelength: 230nm.
The structural identification result is as follows:
1H NMR (400MHz, CDCl
3) δ 7.94 (d, J=8.4Hz, 2H), 7.36 (d, J=8.4Hz, 2H), 4.86-4.80 (m, 1H), (4.52-4.40 m, 2H), 4.37 (dd, J=9.6,8.8Hz, 1H), 2.44 (s, 3H), (1.70-1.46 m, 3H), 1.29-1.10 (m, 3H), (0.83 t, J=7.2Hz, 3H);
13C NMR (100MHz, CDCl
3) δ 152.2,146.2,134.7,130.1,128.5,65.0,60.3,53.9,29.7,29.2,22.0,21.8,13.9.
The conversion of embodiment 18, photolytic activity oxazoline ketone product is derived
(1) bromine is to the Synthesis compound formula VI-a (seeing structural formula VI-a) of nitrine
In reaction flask, add photolytic activity oxazoline ketone product (shown in the formula I-a) (0.1086g, 0.3mmol, 99%ee) and NaN
3(0.0390g, 0.6mmol) adds DMF (3.0mL), is heated to 80 ℃ and stirs 4h.Add water (5mL) cancellation reaction, (3 * 10mL) extractions, (3 * 15mL) wash ethyl acetate, and saturated aqueous common salt (15mL) is washed anhydrous magnesium sulfate drying to merge the organic phase water.(eluent is sherwood oil: ethyl acetate=5/1 v/v), gets 0.0579g white solid azide substitution oxazoline ketone product (shown in the formula VI-a) to 3/1, productive rate 60%, enantiomeric excess 99% (HPLC mensuration) to be spin-dried for rear column chromatography.
The HPLC condition: chirality AS-H post, moving phase: the volume ratio of normal hexane and Virahol is 80: 20 mixed solvent, flow velocity: 1.0mL/min, absorbing wavelength: 230nm.
The structural identification result is as follows:
1H NMR (400MHz, CDCl
3) δ 7.96 (d, J=8.0Hz, 2H), 7.36 (d, J=8.0Hz, 2H), 4.52-4.44 (m, 1H), (4.26 t, J=8.8Hz, 1H), 4.23-4.17 (m, 1H), 4.08-4.01 (m, 1H), 2.43 (s, 3H), 1.57-1.42 (m, 2H), (1.09 t, J=7.2Hz, 3H);
13C NMR (100MHz, CDCl
3) δ 152.2,146.2,134.8,130.1,128.5,64.8,63.1,59.0,24.7,21.8,10.9.
(2) bromine is to the Synthesis compound formula VII-a (seeing structural formula VII-a) of sulphur
In reaction flask, add photolytic activity oxazoline ketone product (shown in the formula I-a) (0.1086g, 0.3mmol, 99%ee) and NaSPh (0.0793g, 0.6mmol), add DMF (3.0mL), be heated to 80 ℃ and stir 12h.Add water (5mL) cancellation reaction, (3 * 10mL) extractions, (3 * 15mL) wash ethyl acetate, and saturated aqueous common salt (15mL) is washed anhydrous magnesium sulfate drying to merge the organic phase water.(eluent is sherwood oil: ethyl acetate=4/1 v/v), gets 0.0816g white solid sulfo-oxazoline ketone product (shown in the formula VII-a), productive rate 69%, enantiomeric excess 99% (HPLC mensuration) to be spin-dried for rear column chromatography.
The HPLC condition: chirality AD-H post, moving phase: the volume ratio of normal hexane and Virahol is 85: 15 mixed solvent, flow velocity: 0.5mL/min, absorbing wavelength: 260nm.
The structural identification result is as follows:
1H NMR (400MHz, CDCl
3) δ 7.83 (d, J=7.6Hz, 2H), 7.41-7.32 (m, 2H), 7.30-7.19 (m, 5H), 4.72-4.64 (m, 1H), 4.34-4.25 (m, 2H), 3.63 (t, J=7.2Hz, 1H), 2.39 (s, 3H), 1.70-1.57 (m, 2H), (1.15 t, J=7.2Hz, 3H);
13C NMR (100MHz, CDCl
3) δ 152.6,145.6,134.9,133.6,132.6,129.9,129.2,128.3,127.7,64.8,59.7,55.4,26.1,21.8,12.0.
(3) bromine is to the Synthesis compound formula VIII-a (seeing structural formula VIII-a) of chlorine
In reaction flask, add photolytic activity oxazoline ketone product (shown in the formula I-a) (0.362g, 1.0mmol, 99%ee) and LiCl (0.0848g, 2.0mmol), add DMF (5.0mL), be heated to 80 ℃ and stir 9h.Add water (10mL) cancellation reaction, (3 * 15mL) extractions, (3 * 15mL) wash ethyl acetate, and saturated aqueous common salt (15mL) is washed anhydrous magnesium sulfate drying to merge the organic phase water.(eluent is sherwood oil: ethyl acetate: methylene dichloride=2/1/1 to be spin-dried for rear column chromatography, v/v/v), get 0.2302g white solid chloro oxazoline ketone product (shown in the formula VIII-a), productive rate 72%, enantiomeric excess 99% (HPLC mensuration).
The HPLC condition: chirality AD-H post, moving phase: the volume ratio of normal hexane and Virahol is 85: 15 mixed solvent, flow velocity: 0.5mL/min, absorbing wavelength: 230nm.
The structural identification result is as follows:
1H NMR (400MHz, CDCl
3) δ 7.97 (d, J=8.0Hz, 2H), 7.36 (d, J=8.0Hz, 2H), 4.69 (td, J=6.4,2.4Hz, 1H), 4.52 (ddd, J=10.0,4.4,2.4Hz, 1H), 4.40-4.35 (m, 2H), 2.45 (s, 3H), 1.80-1.69 (m, 1H), 1.67-1.54 (m, 1H), 1.13 (t, J=7.2Hz, 3H);
13C NMR (100MHz, CDCl
3) δ 152.1,146.0,134.7,129.9,128.8,64.3,63.4,60.1,27.2,22.0,11.5.
(4) be hydrolyzed into ethylenimine (seeing structural formula IX-a)
In reaction flask, be weighed into photolytic activity oxazoline ketone product (shown in the formula I-a) (0.724g, 2.0mmol, 99%ee), add methyl alcohol (40.0mL), add salt of wormwood (1.38g, 10.0mmol) under the stirring at room, room temperature reaction 1h.Add 1N HCl (aq) neutralization, revolve the inspissation contracting, add water (10mL) dilution, use again methylene dichloride (3 * 10mL) extractions, anhydrous magnesium sulfate drying.(eluent is sherwood oil: ethyl acetate=2/1 v/v), gets 0.473g white solid product (shown in the formula IX-a), productive rate 93%, enantiomeric excess 99% (HPLC mensuration) to be spin-dried for rear column chromatography.
The HPLC condition: chirality AS-H post, moving phase: the volume ratio of normal hexane and Virahol is 80: 20 mixed solvent, flow velocity: 1.0mL/min, absorbing wavelength: 230nm.
The structural identification result is as follows:
1H NMR (400MHz, CDCl
3) δ 7.84 (d, J=8.0Hz, 2H), 7.34 (d, J=8.0Hz, 2H), 3.82-3.73 (m, 1H), 3.64-3.56 (m, 1H), 3.05 (td, J=7.2,5.2Hz, 1H), 2.81 (td, J=8.0,5.2Hz, 1H), 2.45 (s, 3H), 1.62-1.38 (m, 3H), 0.86 (t, J=7.2Hz, 3H);
13C NMR (100MHz, CDCl
3) δ 144.7,134.5,129.7,128.0,59.2,46.3,45.1,21.6,20.2,11.6.
(5) the hydrolysate ethylenimine continues to be converted into epoxy compounds (seeing structural formula X-a)
Under the nitrogen protection; NaH (0.048g is being housed; 1.2mmol; 60%) adds photolytic activity ethylenimine (shown in the formula IX-a) (0.0765g and in the reaction flask of THF (2mL); 0.3mmol; THF 99%ee) (1mL) solution, the gained reaction solution is in room temperature reaction 4h.Add saturated NH
4Cl (solution) cancellation reaction, (3 * 5mL) extractions, saturated aqueous common salt (10mL) is washed anhydrous magnesium sulfate drying to use ethyl acetate again.(eluent is sherwood oil: ethyl acetate=4/1 v/v), gets 0.054g white solid epoxy product (shown in the formula X-a), productive rate 71%, enantiomeric excess 99% (HPLC mensuration) to be spin-dried for rear column chromatography.
The HPLC condition: chirality AD-H post, moving phase: the volume ratio of normal hexane and Virahol is 85: 15 mixed solvent, flow velocity: 1.0mL/min, absorbing wavelength: 230nm.
The structural identification result is as follows:
1H NMR (400MHz, CDCl
3) δ 7.76 (d, J=7.6Hz, 2H), 7.29 (d, J=7.6Hz, 2H), 4.89 (d, J=8.4Hz, 1H), 3.47-3.38 (m, 1H), 3.00-2.95 (m, 1H), 2.70-2.64 (m, 1H), 2.64-2.59 (m, 1H), 2.42 (s, 3H), 1.66-1.42 (m, 2H), 0.82 (t, J=7.2Hz, 3H);
13CNMR (100MHz, CDCl
3) δ 143.4,138.3,129.8,127.0,54.3,53.5,44.4,26.6,21.6,10.0.
(6) chloro oxazoline ketone is hydrolyzed into ethylenimine (seeing structural formula XI-a)
In reaction flask, be weighed into photolytic activity oxazoline ketone product (shown in the formula VIII-a) (0.0953g, 0.3mmol, 99%ee), add methyl alcohol (6.0mL), add salt of wormwood (0.0828g, 0.6mmol) under the stirring at room, room temperature reaction 50min (thin plate monitoring).Add 1N HCl (aq) neutralization, revolve the inspissation contracting, add water (5mL) dilution, use again methylene dichloride (3 * 5mL) extractions, anhydrous magnesium sulfate drying.(eluent is sherwood oil: ethyl acetate=2/1 v/v), gets 0.0537g white solid product (shown in the formula XI-a), productive rate 70%, enantiomeric excess 99% (HPLC mensuration) to be spin-dried for rear column chromatography.
The HPLC condition: chirality IC-H post, moving phase: the volume ratio of normal hexane and Virahol is 80: 20 mixed solvent, flow velocity: 1.0mL/min, absorbing wavelength: 230nm.
The structural identification result is as follows:
1H NMR (400MHz, CDCl
3) δ 7.85 (d, J=8.0Hz, 2H), 7.34 (d, J=8.0Hz, 2H), (4.10 ddd, J=12.8,9.2,2.8Hz, 1H), (3.91 ddd, J=12.8,8.0,5.2Hz, 1H), (2.99-2.89 m, 2H), 2.76 (dd, J=9.2,4.8Hz, 1H), 2.45 (s, 3H), 1.77-1.65 (m, 1H), (1.55-1.43 m, 1H), 0.86 (t, J=7.2Hz, 3H);
13C NMR (100MHz, CDCl
3) δ 144.5,137.3,129.8,127.5,61.1,51.8,48.0,23.8,21.8,11.6.
Claims (12)
1. the compound shown in the formula I:
Among the formula I, R is selected from any one in the following radicals: methyl, phenyl and substituted-phenyl; Neighbour in the described substituted-phenyl,, any one or two positions are replaced by following any one group in the contraposition: methyl, nitro, fluorine atom, chlorine atom and bromine atoms;
R
1Be selected from the following radicals any one: hydrogen, alkyl, contain substituent alkyl and cycloalkyl; Described substituting group in the substituent alkyl optional position in alkyl that contains replaces, described substituting group be selected from following any one: phenyl, benzyloxy, ether, ester group, sulphonyl ester group, amido, alkynyl, thiazolinyl, cyano group, fluorine atom, chlorine atom, bromine atoms and iodine atom;
R
2Be selected from hydrogen or alkyl.
2. compound according to claim 1 is characterized in that: described R
1In alkyl or contain the straight or branched alkyl that substituent alkyl is C1-C16; Described R
1In cycloalkyl be the cycloalkyl of C3-C8;
Described R
2In alkyl be the alkyl of C1-C5.
3. compound according to claim 1 and 2, it is characterized in that: among the formula I, R is p-methylphenyl.
4. prepare the method for compound shown in each described formula I among the claim 1-3, comprise the steps: under the katalysis of the title complex that chiral phosphine ligand and metal Lewis acid form, olefin substrate shown in bromine source shown in arbitrary among formula V-a, formula V-b, formula V-c and the formula V-d and the formula II is carried out the bromo-amine cyclization in organic solvent, react the complete compound shown in the formula I that obtains;
R, R among the described formula II
1, R
2Definition cotype I.
5. method according to claim 4 is characterized in that: described chiral phosphine ligand be configured as R, R configuration or S, S configuration;
The structural formula of described chiral phosphine ligand is suc as formula shown in III-a or the formula III-b:
Among described formula III-b, Ar is selected from phenyl or substituted-phenyl, the neighbour in the described substituted-phenyl,, any one or two positions are replaced by following any one group in the contraposition: methoxyl group and methyl;
Described metal Lewis acid is suc as formula shown in the IV:
M (OTf)
x(formula IV)
Among the described formula IV, M represents metallic element, and OTf represents the trifluoromethanesulfonic acid root;
Described M (OTf) x is specially Sc (OTf)
3, Sm (OTf)
3, La (OTf)
3, Y (OTf)
3, Yb (OTf)
3, Cu (OTf)
2, Zn (OTf)
2, Hf (OTf)
3Or Pr (OTf)
3, preferred Sc (OTf)
3
6. according to claim 4 or 5 described methods, it is characterized in that: the concentration of olefin substrate shown in the described formula II in reaction system is 0.05～1 mol/L, preferred 0.07-0.1 mol/L;
The molar ratio of olefin substrate is 1～5: 1 shown in bromine source shown in arbitrary among described formula V-a, formula V-b, formula V-c, the formula V-d and the formula II, preferred 1.2: 1;
Lewis acidic mol ratio shown in chiral ligand shown in the formula III and the formula IV is 0.8～1.5: 1 in the described title complex, preferred 1: 1; The molar ratio of olefin substrate is 0.01～0.2: 1 shown in the title complex that Lewis acid shown in chiral ligand shown in the formula III and the formula IV forms and the formula II, preferred 0.02～0.1: 1.
7. each described method according to claim 4-6 is characterized in that: described organic solvent is selected from least a in benzene, toluene, trichloromethane, ethylene dichloride and the methylene dichloride, and preferred volume ratio is 3: 1 toluene and the mixed solvent of methylene dichloride.
8. each described method according to claim 4-7, it is characterized in that: the temperature of reaction of described reaction is-80 ℃～25 ℃, preferred-50 ℃ to-30 ℃; Reaction times is 18～72 hours, preferred 48～72 hours.
9. the compound shown in arbitrary among the formula VI formula VIII:
Among the formula VI-VIII, R, R
1, R
2Definition cotype I.
10. prepare arbitrary among the claim 9 Chinese style VI-formula VIII shown in the method for compound, comprise the steps: compound shown in the claim 1-3 Chinese style I and nucleophilic reagent are reacted in solvent, obtain arbitrary among the formula VI-formula VIII shown in compound;
Wherein, the used nucleophilic reagent of compound shown in the preparation formula VI is N
3Na or N
3K, the used nucleophilic reagent of compound shown in the preparation formula VII is thiophenol sodium or thiophenol potassium, the used nucleophilic reagent of compound shown in the preparation formula VIII is LiCl, NaCl or KCl;
Described solvent is DMF, methyl-sulphoxide, tetrahydrofuran (THF) or acetone.
11. the method for compound shown in preparation formula IX or the formula XI comprises the steps: compound shown in the claim 1-3 Chinese style I is hydrolyzed under alkaline condition, namely obtains the compound shown in the formula IX;
Compound shown in the claim 9 Chinese style VIII is hydrolyzed under alkaline condition, namely obtains the compound shown in the formula XI;
Wherein, described alkaline condition is provided by following any one alkali: salt of wormwood, yellow soda ash, Quilonum Retard, saleratus, sodium bicarbonate, lithium bicarbonate, potassium hydroxide, sodium hydroxide and lithium hydroxide; Described solvent is methyl alcohol, ethanol, propyl alcohol or Virahol;
Among formula IX and the XI, R, R
1, R
2Definition cotype I; R among the formula IX
1And R
2Be in trans, R among the formula XI
1And R
2Be in cis.
12. the method for compound shown in the preparation formula X comprises the steps:
1) compound shown in the claim 1-3 Chinese style I is hydrolyzed under alkaline condition, namely obtains the compound shown in the formula IX; Or the compound shown in the claim 9 Chinese style VIII is hydrolyzed under alkaline condition, namely obtain the compound shown in the formula XI;
Among formula IX and the XI, R, R
1, R
2Definition cotype I; R among the formula IX
1And R
2Be in trans, R among the formula XI
1And R
2Be in cis;
Wherein, described alkaline condition is provided by following any one alkali: salt of wormwood, yellow soda ash, Quilonum Retard, saleratus, sodium bicarbonate, lithium bicarbonate, potassium hydroxide, sodium hydroxide and lithium hydroxide; Described solvent is methyl alcohol, ethanol, propyl alcohol or Virahol;
2) compound shown in described formula IX or the XI is reacted under the condition that metal hydride exists, obtain compound shown in the formula X;
Among the formula X, R, R
1, R
2Definition cotype I;
Described metal hydride is sodium hydride or potassium hydride KH; Described solvent is tetrahydrofuran (THF) or ether.
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|---|---|---|---|---|
| CN103306134A (en) * | 2013-07-02 | 2013-09-18 | 席敏皓 | Surface treating agent capable of modifying protein fibers and preparation method and usage thereof |
| CN104447606A (en) * | 2014-12-03 | 2015-03-25 | 中国科学院化学研究所 | Synthesis method and application of 2-carbonyl-4-olefin-5-bromo-1,3-oxazine compound |
| CN106588952A (en) * | 2015-10-20 | 2017-04-26 | 中国科学院化学研究所 | 2'-carbonyl-3-bromo-spiro[benzofuran-2,4'-oxazolidine] compounds and preparation method thereof |
| CN111333560A (en) * | 2020-04-13 | 2020-06-26 | 合肥工业大学 | Method for preparing spiro β -lactam |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003106445A1 (en) * | 2002-06-12 | 2003-12-24 | Qsi Pharma A/S | Compounds and methods for controlling bacterial virulence |
| CN101397278B (en) * | 2007-09-27 | 2011-05-25 | 天津药明康德新药开发有限公司 | Method for synthesizing 3-aryl-5-alkenyl oxazoline-2-one |
| CN102249976A (en) * | 2011-06-10 | 2011-11-23 | 中国科学院化学研究所 | Preparation method of optically pure (-)-clausenamide compound |
-
2013
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003106445A1 (en) * | 2002-06-12 | 2003-12-24 | Qsi Pharma A/S | Compounds and methods for controlling bacterial virulence |
| CN101397278B (en) * | 2007-09-27 | 2011-05-25 | 天津药明康德新药开发有限公司 | Method for synthesizing 3-aryl-5-alkenyl oxazoline-2-one |
| CN102249976A (en) * | 2011-06-10 | 2011-11-23 | 中国科学院化学研究所 | Preparation method of optically pure (-)-clausenamide compound |
Non-Patent Citations (3)
| Title |
|---|
| HUANG D.S. ET AL.: "Enantioselective Bromocyclization of Olefins Catalyzed by Chiral Phosphoric Acid", 《ORGANIC LETTERS》 * |
| MCCOMBIE S.W. ET AL.: "Cyclofunctionalisation reactions of epoxyalcohol derivatives. 3. cyclisationacyl migration of N-benzoylcarbamates to stereodefined oxazolidinones. A new diastereospecific route to thiamphenicol", 《TETRAHEDRON LETTERS》 * |
| YANG D. ET AL.: "Lewis acid-catalyzed atom transfer radical cyclization of unsaturated b-keto amides", 《TETRAHEDRON》 * |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103306134A (en) * | 2013-07-02 | 2013-09-18 | 席敏皓 | Surface treating agent capable of modifying protein fibers and preparation method and usage thereof |
| CN104447606A (en) * | 2014-12-03 | 2015-03-25 | 中国科学院化学研究所 | Synthesis method and application of 2-carbonyl-4-olefin-5-bromo-1,3-oxazine compound |
| CN104447606B (en) * | 2014-12-03 | 2016-06-15 | 中国科学院化学研究所 | The synthetic method of a kind of 2-bromo-1,3-piperazine compound of carbonyl-4-alkene-5-and application |
| CN106588952A (en) * | 2015-10-20 | 2017-04-26 | 中国科学院化学研究所 | 2'-carbonyl-3-bromo-spiro[benzofuran-2,4'-oxazolidine] compounds and preparation method thereof |
| CN106588952B (en) * | 2015-10-20 | 2018-07-27 | 中国科学院化学研究所 | The 2 '-bromo- spiral shells of carbonyl -3- [- oxazolidone of benzofuran -2,4 '] class compound and preparation method thereof |
| CN111333560A (en) * | 2020-04-13 | 2020-06-26 | 合肥工业大学 | Method for preparing spiro β -lactam |
| CN111333560B (en) * | 2020-04-13 | 2024-01-23 | 合肥工业大学 | Method for preparing spiro beta-lactam |
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