CN111518010B - Synthesis of bicyclo [3,3,0] cyclooctanone derivatives and preparation method thereof - Google Patents
Synthesis of bicyclo [3,3,0] cyclooctanone derivatives and preparation method thereof Download PDFInfo
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Abstract
The invention discloses a bicyclo [3,3,0] cyclooctanone derivative shown in formula (I) and a synthesis method thereof, eight-membered ring enol is taken as a raw material, and the bicyclo [3,3,0] cyclooctanone derivative shown in formula (I) is synthesized under the action of a catalyst and an additive. The preparation method has the advantages of simple and easily synthesized raw materials, simple and convenient post-treatment, good universality, good yield, environmental friendliness and the like. The bicyclo [3,3,0] cyclooctanone derivatives disclosed by the invention are main structural units in a plurality of natural products and drug molecules, and most of the derivatives have stronger biological activity and have great research value in the aspect of drug synthesis.
Description
Technical Field
The invention belongs to the technical field of organic compound synthesis, and relates to a synthetic method for synthesizing bicyclo [3,3,0] cyclooctanone derivatives through a copper-catalyzed ring contraction reaction.
Background
Five-membered carbocyclic compounds are widely present in various classes of organic compounds. In particular, bicyclo [3,3,0] cyclooctane compounds are key scaffolds for many pharmaceutical and natural products. Based on these, many studies have been made on a method for synthesizing a bicyclo [3,3,0] cyclooctane compound. Conventional methods for synthesizing bicyclo [3,3,0] cyclooctane compounds typically involve intramolecular or intermolecular cyclization reactions as well as cycloaddition reactions. For example: literature (1) Millham, a.b.; kier, m.j.; leon, r.m.; karmakar, r.; stempel, z.d.; micalizio, G.C.org.Lett.2019,21, 567-; huang, Y.Chem.Comm.2014,50, 948-; yang, Z.tetrahedron.2019,75,1746-1750.
In addition, the trans-ring reaction has attracted great interest in constructing a bicyclic system as a third feasible strategy. The trans-ring strategy can increase the complexity of the molecule in a single transition with minimal steps, with superior reaction economics in organic synthesis. For example, document (4) Snider, b.b.; zhou.j, org.lett.2006,8,1283-1286.(5) mat, r.; manzano, r.; reyes, e.; carrillo, l.; uri, u.; vicario, J.L.J.Am.chem.Soc.2019,141,9495-9499, however, the ring contraction strategy is still in the development stage at present, and mainly has the defects of low temperature, complex catalytic system, complex raw material synthesis, limited substrates and the like. Therefore, there is still a need to develop a method for synthesizing bicyclo [3,3,0] cyclooctane compounds which is more economical and efficient, has simple reaction conditions and can be widely applied.
Disclosure of Invention
The invention aims to provide a bicyclo [3,3,0] cyclooctanone derivative and a synthesis method thereof, wherein the synthesis method is a low-cost environment-friendly synthesis method under the catalysis of copper. The bicyclo [3,3,0] cyclooctanone derivatives provided by the invention are main structural units in a plurality of natural products and drug molecules, and most of the derivatives have stronger biological activity and have great research value in the aspect of drug synthesis.
The invention provides an unreported bicyclo [3,3,0] cyclooctanone derivative, which has a structure shown in a formula (I):
wherein;
R1is 3- (1-benzyl) indolyl, alpha-naphthyl, phenyl, 2-furyl, 2-thienyl, 2-pyrrolyl;
R2the compound is phenyl substituted by electron withdrawing or electron donating, wherein the electron withdrawing group is halogen or nitro, and the electron donating group is alkyl or alkoxy.
Preferably, the first and second electrodes are formed of a metal,
R1is 3- (1-benzyl) indolyl, alpha-naphthyl, phenyl, 2-furyl, 2-thienyl, 2-pyrrolyl;
R2is phenyl, nitro substituted phenyl, halogen substituted phenyl, C1-C10 alkyl substituted phenyl, C1-C10 alkoxy substituted phenyl.
It is further preferred that the first and second liquid crystal compositions,
R1is 3- (1-benzyl) indolyl, alpha-naphthyl, phenyl, 2-furyl, 2-thienyl, 2-pyrroleA group;
R2is phenyl, p-chlorophenyl, m-nitrophenyl, p-methoxyphenyl, p-methylphenyl.
The invention also provides a synthesis method of the bicyclo [3,3,0] cyclooctanone derivatives, which comprises the steps of taking the octatomic enol as a raw material in a solvent, and synthesizing to obtain the bicyclo [3,3,0] cyclooctanone derivatives under the action of an acidic additive and a catalyst; the reaction process is shown as the formula (II):
wherein the content of the first and second substances,
R1is 3- (1-benzyl) indolyl, alpha-naphthyl, phenyl, 2-furyl, 2-thienyl, 2-pyrrolyl;
R2the compound is phenyl substituted by electron withdrawing or electron donating, the electron withdrawing group is halogen or nitro, and the electron donating group is alkyl or alkoxy.
Preferably, the first and second electrodes are formed of a metal,
R1is 3- (1-benzyl) indolyl, alpha-naphthyl, phenyl, 2-furyl, 2-thienyl, 2-pyrrolyl;
R2is phenyl, nitro substituted phenyl, halogen substituted phenyl, C1-C10 alkyl substituted phenyl, C1-C10 alkoxy substituted phenyl.
It is further preferred that the first and second liquid crystal compositions,
R1is 3- (1-benzyl) indolyl, alpha-naphthyl, phenyl, 2-furyl, 2-thienyl, 2-pyrrolyl;
R2is phenyl, p-chlorophenyl, m-nitrophenyl, p-methoxyphenyl, p-methylphenyl.
Wherein the acidic additive comprises HCl and CH3COOH、TsOH、TfOH。
Wherein the catalyst comprises CuCl, CuI and CuCl2、Cu(OTf)2。
Wherein the solvent is N, N-dimethylformamide, N-dimethylacetamide and dimethyl sulfoxide.
Wherein the temperature of the reaction is 100 ℃.
Wherein the reaction time is 6 hours.
Wherein the mol ratio of the eight-membered cyclic enol to the acidic additive to the catalyst is 1: 4: 0.2.
the invention is preferably carried out under nitrogen protection.
In a specific embodiment, the synthesis method of the bicyclo [3,3,0] cyclooctanone derivatives comprises the steps of taking octatomic enol as a raw material under the protection of nitrogen, and synthesizing to obtain the bicyclo [3,3,0] cyclooctanone derivatives shown in the formula (I) under the action of an acidic additive and a catalyst; the reaction process is shown as the formula (II'):
wherein R is1、R2Is as defined in formula (II).
The invention has the beneficial effects that: the synthesis method has the advantages of simple and easy synthesis of raw materials, simple and convenient post-treatment, good universality, good yield (50-90%), environmental friendliness and the like. The bicyclo [3,3,0] cyclooctanone derivatives provided by the invention are main structural units in a plurality of natural products and drug molecules, and most of the derivatives have stronger biological activity and have great research value in the aspect of drug synthesis.
Detailed Description
The present invention will be described in further detail with reference to the following specific examples. The procedures, conditions, implementation methods and the like for carrying out the present invention are general knowledge and well-known attempts in the art, except for those specifically mentioned below, and the present invention is not particularly limited thereto.
Example 1: synthesis of IA
The eight-membered ring ketene, the acid, the catalyst and the solvent respectively adopt (1E,3Z) -ethyl-3- (1-benzyl-1H-indole-3-carbonyl) -4-hydroxy-2-phenylcyclooctane-1, 3-diene formate, alkene hydrochloric acid, CuCl and dimethyl sulfoxide (DMSO), the dosage of the raw materials respectively is 0.20mmol of eight-membered ring enol (1E,3Z) -ethyl-3- (1-benzyl-1H-indole-3-carbonyl) -4-hydroxy-2-phenylcyclooctane-1, 3-diene formate, 0.8mmol of diluted hydrochloric acid, 0.04mmol of CuCl and 5mL of the solvent, the reaction is carried out for 6 hours at 100 ℃ to obtain the target product, namely the formula (IA), a white solid, and the isolation yield is 84%. mp 164-.
Nuclear magnetic data:
1H NMR(500MHz,Chloroform-d)δ8.49(d,J＝8.0Hz,1H),7.54(s,1H),7.42-7.40(m,2H),7.31-7.15(m,9H),6.83(d,J＝7.3Hz,2H),5.14(q,J＝15.7Hz,2H),4.21(q,J＝7.1Hz,2H),3.10(dd,J＝9.5,3.1Hz,1H),2.59-2.53(m,1H),2.06-1.94(m,2H),1.87-1.81(m,2H),1.58-1.48(m,1H),1.16(t,J＝7.1Hz,3H).13C NMR(126MHz,CDCl3)δ205.36,186.59,174.10,168.60,142.35,138.23,137.13,135.18,132.46,130.48,128.87,128.84,128.78,128.00,126.65,126.37,123.77,122.99,122.91,116.67,110.07,63.37,61.85,58.75,50.66,32.49,29.48,25.56,14.08.
high resolution mass spectral data: HRMS (ESI) calcd for C33H30NO4[M+H]+:504.2169；found:504.2189.
Example 2: synthesis of IB
The eight-membered ketene, the acid, the catalyst and the solvent respectively select (1E,3Z) -ethyl-4-hydroxy-2-phenyl-3- (1-p-methyl benzenesulfonyl-1H-pyrrole-3-carbonyl) cyclooctane-1, 3-diene formate, alkene hydrochloric acid, CuCl and dimethyl sulfoxide (DMSO), the raw materials respectively comprise 0.20mmol of eight-membered enol (1E,3Z) -ethyl-4-hydroxy-2-phenyl-3- (1-p-methyl benzenesulfonyl-1H-pyrrole-3-carbonyl) cyclooctane-1, 3-diene formate, 0.8mmol of dilute hydrochloric acid, 0.04mmol of CuCl and 5mL of solvent, the reaction is carried out at 100 ℃ for 6 hours to obtain a target product formula (IB) and a yellow solid, the isolation yield was 50%. mp 162-.
Nuclear magnetic data:
1H NMR(400MHz,Chloroform-d)δ8.02(d,J＝8.3Hz,2H),7.72-7.71(m,1H),7.37-7.09(m,6H),6.86-6.85(m,1H),6.12(t,J＝3.4Hz,1H),4.32-4.19(m,2H),3.05-3.02(m,1H),2.62-2.54(m,1H),2.45(s,3H),2.31(s,3H),1.88-1.78(m,2H),1.68-1.56(m,1H),1.51-1.40(m,1H),1.29-1.20(m,4H).13C NMR(100MHz,CDCL3)δ205.11,180.40,174.48,171.68,145.35,142.33,139.66,135.80,133.35,131.24,129.94,129.73,129.70,128.95,128.92,126.97,110.69,62.99,61.98,58.63,32.44,29.15,25.27,21.45,21.17,13.72.
high resolution mass spectral data: HRMS (ESI) calcd for C30H30NO6S[M+H]+:532.1788；found:532.18042.
Example 3: synthesis of IC
The eight-membered ring ketene, the acid, the catalyst and the solvent respectively adopt (1E,3Z) -ethyl-3- (furan-3-carbonyl) -4-hydroxy-2-phenylcyclooctane-1, 3-diene formate, alkene hydrochloric acid, CuCl and dimethyl sulfoxide (DMSO), the dosage of the raw materials respectively is 0.20mmol of eight-membered ring enol (1E,3Z) -ethyl-4-hydroxy-2-phenyl-3- (1-p-methyl benzenesulfonyl-1H-pyrrole-3-carbonyl) cyclooctane-1, 3-diene formate, 0.8mmol of dilute hydrochloric acid, 0.04mmol of CuCl and 5mL of the solvent, and the raw materials react at 100 ℃ for 6 hours to obtain a target product formula (IC) and a yellow oily substance with the separation yield of 77%.
Nuclear magnetic data:
1H NMR(500MHz,Chloroform-d)δ7.54(s,1H),7.38-7.28(m,5H),7.06(d,J＝3.5Hz,1H),6.40(dd,J＝3.5,1.5Hz,1H),4.33-4.21(m,2H),3.14(dd,J＝9.4,3.1Hz,1H),2.65-2.59(m,1H),2.06-1.83(m,4H),1.61-1.52(m,1H),1.22(t,J＝7.1Hz,3H).13C NMR(126MHz,CDCl3)δ204.61,180.03,173.55,171.49,151.93,147.95,139.84,132.14,131.03,128.87,121.21,112.40,63.67,62.00,58.79,32.65,29.42,25.54,13.97.
high resolution mass spectral data: HRMS (ESI) calcd for C22H21O5[M+H]+:365.1383；found:365.1394.
Example 4: synthesis of ID
The eight-membered ketene, the acid, the catalyst and the solvent respectively adopt (1E,3Z) -ethyl-3- (thiophene-3-carbonyl) -4-hydroxy-2-phenylcyclooctane-1, 3-diene formate, alkene hydrochloric acid, CuCl and dimethyl sulfoxide (DMSO), the dosage of the raw materials respectively is 0.20mmol of eight-membered enol (1E,3Z) -ethyl-4-hydroxy-2-phenyl-3- (1-p-methyl benzenesulfonyl-1H-pyrrole-3-carbonyl) cyclooctane-1, 3-diene formate, 0.8mmol of dilute hydrochloric acid, 0.04mmol of CuCl and 5mL of the solvent, and the raw materials react at 100 ℃ for 6 hours to obtain the target product formula (ID) and yellow oily matter with the separation yield of 71%.
Nuclear magnetic data:
1H NMR(500MHz,Chloroform-d)δ7.62-7.61(m,1H),7.57-7.56(m,1H),7.41-7.39(m,2H),7.36-7.28(m,3H),6.97-6.95(m,1H),4.36-4.23(m,2H),3.16(dd,J＝9.3,3.2Hz,1H),2.66-2.60(m,1H),2.02-1.85(m,4H),1.62-1.52(m,1H),1.24(t,J＝7.1Hz,3H).13C NMR(126MHz,CDCl3)δ204.51,185.35,173.52,170.21,143.22,140.61,135.55,134.97,131.91,130.99,128.80,128.67,128.06,63.48,61.97,58.66,32.51,29.34,25.49,13.92.
high resolution mass spectral data: HRMS (ESI) calcd for C22H21O4S[M+H]+:381.1155；found:381.1165.
Example 5: synthesis of IE
The eight-membered ring ketene, the acid, the catalyst and the solvent respectively adopt (1E,3Z) -ethyl-3- (1-naphthyl) -4-hydroxy-2-phenylcyclooctane-1, 3-diene formate, alkene hydrochloric acid, CuCl and dimethyl sulfoxide (DMSO), the dosage of the raw materials respectively is 0.20mmol of eight-membered ring enol (1E,3Z) -ethyl-4-hydroxy-2-phenyl-3- (1-p-methyl benzenesulfonyl-1H-pyrrole-3-carbonyl) cyclooctane-1, 3-diene formate, 0.8mmol of dilute hydrochloric acid, 0.04mmol of CuCl and 5mL of the solvent, and the raw materials react for 6 hours at 100 ℃ to obtain the target product formula (IE), a yellow solid and the separation yield is 79%. mp 115 and 117 ℃.
Nuclear magnetic data:
1H NMR(500MHz,Chloroform-d)δ9.18(d,J＝8.7Hz,1H),7.93(t,J＝7.1Hz,2H),7.81(d,J＝7.8Hz,1H),7.66(t,J＝7.7Hz,1H),7.53(t,J＝7.4Hz,1H),7.36–7.29(m,3H),7.21-7.14(m,3H),4.36-4.23(m,2H),3.20-3.18(m,1H),2.65-2.59(m,1H),2.09-1.87(m,4H),1.66-1.56(m,1H),1.27(t,J＝7.1Hz,3H).13C NMR(125MHz,CDCl3)δ205.26,195.33,173.69,169.96,142.71,134.73,133.76,132.43,132.41,132.13,130.82,130.66,128.80,128.63,128.52,128.34,126.55,125.88,124.08,63.53,61.94,58.59,32.46,29.46,25.60,14.02.
high resolution mass spectral data: HRMS (ESI) calcd for C28H25O5[M+H]+:425.1747；found:425.1759.
Example 6: synthesis of IF
The eight-membered ring ketene, the acid, the catalyst and the solvent are respectively selected from (1E,3Z) -ethyl-3-phenyl-4-hydroxy-2-phenylcyclooctane-1, 3-diene formate, alkene hydrochloric acid, CuCl and dimethyl sulfoxide (DMSO), the raw materials are respectively 0.20mmol of eight-membered ring enol (1E,3Z) -ethyl-3-phenyl-4-hydroxy-2-phenylcyclooctane-1, 3-diene formate, 0.8mmol of diluted hydrochloric acid, 0.04mmol of CuCl and 5mL of solvent, and the reaction is carried out at 100 ℃ for 6 hours to obtain the target product of formula (IF) and yellow oily matter with the separation yield of 76%.
Nuclear magnetic data:
1H NMR(500MHz,Chloroform-d)δ7.91(d,J＝7.5Hz,2H),7.49(t,J＝7.3Hz,1H),7.36-7.24(m,7H),4.38-4.23(m,2H),3.17(dd,J＝9.3,3.3Hz,1H),2.66-2.60(m,1H),2.07-1.86(m,4H),1.63-1.54(m,1H),1.27(t,J＝7.1Hz,3H).13C NMR(126MHz,CDCl3)δ205.10,193.76,173.71,170.02,141.04,135.68,133.94,132.01,130.93,129.29,128.81,128.73,128.54,63.59,62.02,58.69,32.50,29.47,25.57,13.99.
high resolution mass spectral data: HRMS (ESI) calcd for C24H23O4[M+H]+:375.1591；found:375.1601.
Example 7: synthesis of IG
The eight-membered ketene, the acid, the catalyst and the solvent respectively adopt (1E,3Z) -ethyl-3- (1-benzyl-1H-indole-3-carbonyl) -4-hydroxy-2- (4-chlorphenyl) cyclooctane-1, 3-diene formate, alkene hydrochloric acid, CuCl and dimethyl sulfoxide (DMSO), the consumption of the raw materials respectively adopts (1E,3Z) -ethyl-3- (1-benzyl-1H-indole-3-carbonyl) -4-hydroxy-2- (4-chlorphenyl) cyclooctane-1, 3-diene formate 0.20mmol, diluted hydrochloric acid 0.8mmol, CuCl 0.04mmol and the solvent 5mL, the reaction is carried out for 6 hours at 100 ℃ to obtain the target product, namely the formula (IG), a yellow solid, and the isolated yield is 89%. mp 185 and 187 ℃.
Nuclear magnetic data:
1H NMR(500MHz,Chloroform-d)δ8.48(d,J＝7.9Hz,1H),7.52(s,1H),7.35-7.18(m,10H),6.86-6.84(m,2H),5.22-5.11(m,2H),4.21(q,J＝7.1Hz,2H),3.11(dd,J＝9.3,3.4Hz,1H),2.59-2.53(m,1H),2.06-1.95(m,2H),1.87-1.80(m,2H),1.57-1.47(m,1H),1.18(t,J＝7.1Hz,3H).13C NMR(125MHz,CDCl3)δ205.06,186.25,173.96,167.00,142.64,138.19,137.18,136.72,135.16,130.92,130.12,129.09,128.92,128.12,126.62,126.26,123.95,123.14,122.86,116.58,110.15,63.32,61.98,58.80,50.68,32.49,29.47,25.62,14.11.
high resolution mass spectral data: HRMS (ESI) calcd for C33H29ClNO4[M+H]+:538.1780；found:538.1799.
Example 8: synthesis of IH
The eight-membered ring ketene, the acid, the catalyst and the solvent respectively adopt (1E,3Z) -ethyl-3- (1-benzyl-1H-indole-3-carbonyl) -4-hydroxy-2- (3-nitrophenyl) cyclooctane-1, 3-diene formate, alkene hydrochloric acid, CuCl and dimethyl sulfoxide (DMSO), the consumption of the raw materials respectively adopts (1E,3Z) -ethyl-3- (1-benzyl-1H-indole-3-carbonyl) -4-hydroxy-2- (3-nitrophenyl) cyclooctane-1, 3-diene formate 0.20mmol, diluted hydrochloric acid 0.8mmol, CuCl 0.04mmol and solvent 5mL, the reaction was carried out at 100 ℃ for 6 hours to obtain the desired product of formula (IH) as a white solid in an isolated yield of 78%. mp 164-.
Nuclear magnetic data:
1H NMR(600MHz,Chloroform-d)δ8.41(d,J＝7.8Hz,1H),8.18(s,1H),8.11(d,J＝8.0Hz,1H),7.77(d,J＝7.8Hz,1H),7.55(s,1H),7.40(t,J＝8.0Hz,1H),7.29-7.22(m,6H),6.93(d,J＝6.8Hz,2H),5.23-5.14(m,2H),4.32-4.24(m,2H),3.18(dd,J＝8.3,4.4Hz,1H),2.57-2.52(m,1H),2.05-1.99(m,2H),1.89-1.79(m,2H),1.59-1.51(m,1H),1.25(t,J＝7.1Hz,3H).13C NMR(150MHz,CDCl3)δ204.95,185.22,173.40,165.76,148.06,144.63,138.03,137.24,135.08,134.98,134.33,129.89,128.87,128.22,126.81,126.03,124.64,124.04,123.23,122.67,122.29,116.66,110.18,63.73,62.30,58.58,50.67,32.23,29.54,25.58,14.07.
high resolution mass spectral data: HRMS (ESI) calcd for C33H29N2O6[M+H]+:549.2020；found:549.2038.
Example 9: synthesis of II
The eight-membered ring ketene, the acid, the catalyst and the solvent respectively adopt (1E,3Z) -ethyl-3- (1-benzyl-1H-indole-3-carbonyl) -4-hydroxy-2- (4-methylphenyl) cyclooctane-1, 3-diene formate, alkene hydrochloric acid, CuCl and dimethyl sulfoxide (DMSO), the consumption of the raw materials respectively adopts (1E,3Z) -ethyl-3- (1-benzyl-1H-indole-3-carbonyl) -4-hydroxy-2- (4-methylphenyl) cyclooctane-1, 3-diene formate 0.20mmol, diluted hydrochloric acid 0.8mmol, CuCl 0.04mmol, CuCl 0.20mmol, 5mL of solvent is used for reacting for 6 hours at 100 ℃ to obtain the target product, namely the formula (II), white solid, and the isolation yield is 84%. mp 184 and 186 ℃.
Nuclear magnetic data:
1H NMR(500MHz,Chloroform-d)δ8.51(d,J＝7.9Hz,1H),7.55(s,1H),7.32-7.15(m,8H),7.03(d,J＝8.1Hz,2H),6.85(d,J＝7.3Hz,2H),5.13(q,J＝15.8Hz,2H),4.20(q,J＝7.1Hz,2H),3.09(dd,J＝9.5,3.1Hz,1H),2.60-2.54(m,1H),2.27(s,3H),2.01-1.93(m,2H),1.87-1.80(m,2H),1.57-1.47(m,1H),1.16(t,J＝7.1Hz,3H).13C NMR(125MHz,CDCl3)δ205.32,186.93,174.26,168.62,141.58,141.09,138.27,137.11,135.24,129.50,128.98,128.80,127.97,126.64,126.40,123.71,122.93,122.91,116.65,110.06,63.21,61.80,58.73,50.64,32.59,29.42,25.55,21.32,14.09.
high resolution mass spectral data: HRMS (ESI) calcd for C34H32NO4[M+H]+:518.2326；found:518.2338.
Example 10: synthesis of IJ
The eight-membered ring ketene, the acid, the catalyst and the solvent respectively adopt (1E,3Z) -ethyl-3- (1-benzyl-1H-indole-3-carbonyl) -4-hydroxy-2- (4-methoxyphenyl) cyclooctane-1, 3-diene formate, alkene hydrochloric acid, CuCl and dimethyl sulfoxide (DMSO), the consumption of the raw materials respectively adopts (1E,3Z) -ethyl-3- (1-benzyl-1H-indole-3-carbonyl) -4-hydroxy-2- (4-methoxyphenyl) cyclooctane-1, 3-diene formate 0.20mmol, diluted hydrochloric acid 0.8mmol, CuCl 0.04mmol, CuCl 0.20mmol, 5mL of solvent is used for reacting for 6 hours at 100 ℃ to obtain the target product, namely the formula (IJ), white solid, and the isolation yield is 90%. mp 188-.
Nuclear magnetic data:
1H NMR(500MHz,Chloroform-d)δ8.52(d,J＝7.8Hz,1H),7.55(s,1H),7.40(d,J＝8.8Hz,2H),7.30-7.15(m,6H),6.82(d,J＝7.1Hz,2H),6.73(d,J＝8.8Hz,2H),5.13(q,J＝15.8Hz,2H),4.24-4.15(m,2H),3.72(s,3H),3.08(dd,J＝9.3,2.7Hz,1H),2.63-2.57(m,1H),2.01-1.81(m,4H),1.56-1.47(m,1H),1.15(t,J＝7.1Hz,3H).13C NMR(125MHz,CDCl3)δ205.10,187.24,174.40,168.07,161.36,140.34,138.28,137.08,135.23,131.07,128.75,127.93,126.56,126.38,124.52,123.67,122.88,122.84,116.50,114.16,110.09,63.00,61.75,58.76,55.18,50.59,32.79,29.30,25.58,14.07.
high resolution mass spectral data: HRMS (ESI) calcd for C34H32NO5[M+H]+:534.2275；found:534.2297.
The protection of the present invention is not limited to the above embodiments. Variations and advantages that may occur to those skilled in the art may be incorporated into the invention without departing from the spirit and scope of the inventive concept, and the scope of the appended claims is intended to be protected.
Claims (5)
1. A synthetic method of bicyclo [3,3,0] cyclooctanone derivatives is characterized in that octacyclic enol is taken as a raw material in a solvent, and the bicyclo [3,3,0] cyclooctanone derivatives shown in the formula (I) are synthesized under the action of an acidic additive and a catalyst; the reaction process is shown as the formula (II):
wherein the content of the first and second substances,
R1is 3- (1-benzyl) indolyl, alpha-naphthyl, phenyl, 2-furyl, 2-thienyl, 2-pyrrolyl;
R2the compound is phenyl substituted by electron withdrawing or electron donating, wherein the electron withdrawing group is halogen or nitro, and the electron donating group is alkyl or alkoxy;
the acidic additive is selected from HCl and CH3COOH；
Said catalysisThe agent is selected from CuCl, CuI and CuCl2。
2. The method of synthesis according to claim 1, wherein the solvent is N, N-dimethylformamide, N-dimethylacetamide or dimethylsulfoxide.
3. The method of synthesis according to claim 1, wherein the temperature of the reaction is 100 ℃.
4. The method of synthesis according to claim 1, wherein the reaction time is 6 hours.
5. The synthetic method of claim 1 wherein the eight-membered ring enol, the acidic additive and the catalyst are in a molar ratio of 1: 4: 0.2.
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