CN113582886A - Penta-substituted 3-alkenylene cyclopentene derivative and synthetic method and application thereof - Google Patents
Penta-substituted 3-alkenylene cyclopentene derivative and synthetic method and application thereof Download PDFInfo
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Abstract
The invention discloses a penta-substituted 3-alkenylene cyclopentene derivative and a synthesis method thereof, wherein the synthesis method comprises the following specific steps: the penta-substituted 3-alkenylene cyclopentene derivative shown in the formula (I) is obtained by taking 3-methyl-3-butene-1-alkynylamine compounds and alkynol compounds as raw materials, adding an organic solvent and a catalyst in an atmosphere of protective gas, and carrying out catalytic synthesis. The preparation method has the advantages of simple and easily obtained raw materials, mild reaction conditions, good substrate universality, high atom economy, high reaction yield, simple post-treatment, environmental friendliness and the like. The invention also discloses application of the penta-substituted 3-alkenylene cyclopentene derivative shown in the formula (I) in synthesis and modification of related natural products and drug molecules.
Description
Technical Field
The invention belongs to the field of organic compound synthesis, and particularly relates to a penta-substituted 3-alkenylene cyclopentene derivative, and a synthesis method and application thereof
Background
The 3-alkenylene cyclopentene derivatives are important organic compounds, are core frameworks of a plurality of natural products and drug molecules, and have wide physiological and pharmacological effects. In addition, the 3-alkenylene cyclopentene derivatives can be used as organic synthesis intermediates due to the conjugated double bonds in the molecules, are convenient for further derivatization, are convenient for synthesis and modification of related drug molecules, natural products and functional materials, and have important practical significance. At present, the efficient construction methods related to the structure are few, and the efficient construction methods are mainly obtained by intermolecular and intramolecular tandem cyclization reactions around a allene/alkyne substrate, such as [1] Deng, Y.Q.; bartholomeyzik, t.; persson, a.k.; sun, j.l.; backvall, j.e. angelw.chem.int.ed., 2012,51, 2703-; [2] vola, c.m.r.; backvall, j.e.. angelw.chem.int.ed., 2013,52, 14209-; [3] vola, c.m.r.; mazuela, j.; backval, J.E. chem.Eur.J.,2014,20, 7608-7612; [4] bartholomeyzik, t.; mazuela, j.; pendrill, r.; deng, y.q.; backvall, j.e. angelw.chem.int.ed., 2014,53, 8696-; [5] bartholomeyzik, t.; pendrill, r.; lihammar, r.; jiang, t.; widmalm, g.; backval, J.E. J.Am.chem.Soc.,2018,140,298-
In the above reported synthesis methods, there are major problems: 1) most of reaction substrates are allene/alkyne, raw materials are not easy to obtain, multi-step synthesis is needed, and the stability is poor; 2) more than equivalent oxidant is needed, the treatment after reaction is relatively complex, and the method is not environment-friendly; 3) some reactions have too long reaction time, which is up to 36 hours; 4) the yield and universality of the reaction need to be further improved; the above synthesis method has certain limitations in view of cost and environmental protection. In addition, these methods have difficulty in directly constructing 3-alkenylene cyclopentenes, and in particular, in introducing a carbamoylmethyl group at the 5-position, which can be further derivatized.
Disclosure of Invention
The invention aims to provide a penta-substituted 3-alkenylene cyclopentene derivative and a synthesis method thereof, and provides a synthesis method of the penta-substituted 3-alkenylene cyclopentene derivative, which has the advantages of mild reaction conditions, high atom economy, high yield, wide universality and environmental friendliness.
The invention provides a penta-substituted 3-alkenylene cyclopentene derivative, which has a structure shown in a formula (I):
in the formula (I), R1Is aryl, C1-C10 alkyl or C1-C10 cycloalkyl; r2Is alkylsulfonyl or arylsulfonyl; r3Is aryl or C1-C10 alkyl.
The invention also provides a synthesis method of the penta-substituted 3-alkenylene cyclopentene derivative, which comprises the following steps: taking 3-methyl-3-butene-1-alkynylamine compounds and alkynol compounds as raw materials, adding an organic solvent and a catalyst, and catalytically synthesizing to obtain pentasubstituted 3-alkenylene cyclopentene derivatives shown in the formula (I);
the reaction process is shown as the formula (II):
in the formula (II), R1Is aryl, C1-C10 alkyl or C1-C10 cycloalkyl; r2Is alkylsulfonyl or arylsulfonyl; r3Is aryl or C1-C10 alkyl.
Preferably, R1Is methyl, ethyl, benzyl, cyclopropyl, cyclopentyl; r2P-toluenesulfonyl and methanesulfonyl; r3Is phenyl, 4-chlorphenyl, 4-bromophenyl, 4-nitrophenyl, 4-esterylphenyl, 4-methylphenyl, 4-methoxyphenyl, 9-phenanthryl, n-butyl.
Preferably, the catalyst is selected from PPh3AuNTf2、PPh3AuBF4、PPh3AuSbF6、PPh3AuOTf PPh3AuCl and PtCl2One or more of (a).
Preferably, the organic solvent is selected from one or more of 1, 2-dichloroethane, dichloromethane, 1, 4-dioxane, acetonitrile, toluene and chloroform.
Preferably, the 3-methyl-3-butene-1-alkynylamine compound: alkynol compounds: the molar ratio of the catalyst is 1: (1-2): (0.05-0.5).
Preferably, the temperature of the reaction is 20-50 ℃.
Preferably, the reaction time is 2-6 h.
Preferably, the protective gas is nitrogen or argon.
The invention also provides application of the penta-substituted 3-alkenylene cyclopentene derivative in synthesis and modification of related natural products and active drug molecules.
In a specific embodiment, in the preparation method, 3-methyl-3-butene-1-alkynylamine compounds and alkynol compounds are used as raw materials in a nitrogen atmosphere, and PPh is used3AuOTf is used as a catalyst, 1, 2-Dichloroethane (DCE) is used as a solvent, and pentasubstituted 3-alkenylene cyclopentene derivatives shown in the formula (I) are synthesized at 25 ℃, as shown in the following reaction formula (III):
wherein R is1Is aryl, C1-C10 alkyl or C1-C10 cycloalkyl; r2Is alkylsulfonyl or arylsulfonyl; r3Is aryl or C1-C10 alkyl.
Wherein, the 3-methyl-3-butene-1-alkynylamine compounds: alkynol compounds: PPh3Molar ratio of AuOTf 1: 1.2: 0.1.
wherein the reaction time is 2-6 h.
The invention has the beneficial effects that: the structure of the penta-substituted 3-alkenylene cyclopentene derivative is introduced with carbamoylmethyl, which is convenient for further derivatization and synthesis and modification of related drug molecules. The synthesis method of the penta-substituted 3-alkenylene cyclopentene derivative uses Au/Ag co-catalysis, and has the advantages of simple synthesis of reaction raw materials, mild reaction conditions, excellent yield, high atom economy, good reaction substrate universality, simple and convenient post-treatment and environmental friendliness.
Detailed Description
In order to make the technical problems, technical solutions and advantageous effects solved by the present invention more apparent, the present invention is further described in detail below with reference to the following embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention. 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. The procedures, conditions, reagents, experimental methods and the like for carrying out the present invention are general knowledge and common general knowledge in the art except for the contents specifically mentioned below, and the present invention is not particularly limited.
Wherein Ts is p-toluenesulfonyl.
Example 1:
synthesis of 1-phenyl-5-methyl-5- (N-methyl-N-Ts carbamoylmethyl) -3- (2-propenylene) cyclopentene (IA)
Under nitrogen atmosphere, 0.3mmol of 3-methyl-3-butene-1-alkynylamine compound, 0.36mmol of alkynol, 3mL of 1, 2-dichloroethane, and PPh were added to a 10 mL reaction tube3AuCl 0.03mmol and AgOTf 0.03 mmol. The reaction was carried out at 25 ℃ for 6 hours to give the desired product of formula (IA) as a pale yellow oily liquid in an isolated yield of 80%.
Nuclear magnetic data of the product: 1H NMR (400MHz, CDCl)3):δ7.55(d,J＝8.2Hz,2H),7.20-7.27(m,7H),6.39(s,1H),3.21(s,3H),3.07(d,J＝17.1Hz,1H),2.74(d,J＝17.0Hz,1H),2.72(d,J＝15.7Hz,1H),2.48(d,J＝16.2Hz,1H),2.40(s,3H),1.77(s,3H),1.67(s,3H),1.31(s,3H)；13C NMR(100MHz,CDCl3):δ171.5,152.6,144.5,137.3,136.5,136.4,129.8,128.6,128.1,127.5,127.1,126.9,122.8,48.4,44.9,44.3,32.9,26.9,21.5,21.2,20.6。
High resolution mass spectral data: HRMS (ESI, m/z) calcd.for C25H29NNaO3S[M+Na]+calc.:446.1766；found:446.1759。
Example 2:
synthesis of 1- (4-bromophenyl) -5-methyl-5- (N-methyl-N-Ts carbamoylmethyl) -3- (2-propenylene) cyclopentene (IB)
Under nitrogen atmosphere, 0.3mmol of 3-methyl-3-butene-1-alkynylamine compound, 0.36mmol of alkynol, 3mL of 1, 2-dichloroethane, and PPh were added to a 10 mL reaction tube3AuCl 0.03mmol and AgOTf 0.03 mmol. The reaction was carried out at 25 ℃ for 5 hours to obtain the desired product of formula (IB) as a pale yellow oily liquid in an isolated yield of 70%.
Nuclear magnetic data of the product: 1H NMR (400MHz, CDCl)3):δ7.48(d,J＝8.2Hz,2H),7.30(d,J＝8.4Hz,2H),7.18(d,J＝8.2Hz,2H),7.05(d,J＝8.4Hz,2H),3.15(s,3H),2.95(d,J＝17.2Hz,1H),2.68(d,J＝17.2,2H),2.37-2.41(m,4H),1.71(s,3H),1.60(s,3H),1.22(s,3H)；13C NMR(100MHz,CDCl3):δ171.3,151.0,144.7,136.4,136.2,136.2,131.2,129.9,129.2,129.1,127.0,123.7,120.8,48.3,44.8,44.3,32.9,27.2,21.6,21.3,20.7。
High resolution mass spectral data: HRMS (ESI, m/z) calcd.for C25H28BrNNaO3S[M+Na]+calc.:524.0871；found:524.0864。
Example 3:
synthesis of 1- (4-nitrophenyl) -5-methyl-5- (N-methyl-N-Ts carbamoylmethyl) -3- (2-propenylidene) cyclopentene (IC)
Under nitrogen atmosphere, 0.3mmol of 3-methyl-3-butene-1-alkynylamine compound, 0.36mmol of alkynol, 3mL of 1, 2-dichloroethane, and PPh were added to a 10 mL reaction tube3AuCl 0.03mmol and AgOTf 0.03 mmol. The reaction was carried out at 25 ℃ for 4 hours to give the desired product of formula (IC) as a pale yellow oily liquid in an isolated yield of 75%.
Nuclear magnetic data of the product: 1H NMR (400MHz, CDCl)3):δ8.00(d,J＝8.9Hz,2H),7.55(d,J＝8.4Hz,2H),7.37(d,J＝9.0Hz,2H),7.21(d,J＝8.1Hz,2H),6.59(s,1H),3.10-3.14(m,4H),2.78(d,J＝17.2Hz,1H),2.72(d,J＝16.0Hz,1H),2.36-2.43(m,4H),1.77(s,3H),1.64(s,3H),1.32(s,3H)；13C NMR(100MHz,CDCl3):δ170.9,149.5,146.1,144.9,143.9,136.2,136.0,131.7,129.8,127.4,126.9,126.5,123.3,48.2,44.6,44.5,32.8,27.5,21.4,21.4,20.7。
High resolution mass spectral data: HRMS (ESI, m/z) calcd.for C25H29N2O5S[M+H]+calc.:469.1797；found:469.1784。
Example 4:
synthesis of 1- (4-ethoxyformylphenyl) -5-methyl-5- (N-methyl-N-Ts carbamoylmethyl) -3- (2-propenylene) cyclopentene (ID)
Under nitrogen atmosphere, 0.3mmol of 3-methyl-3-butene-1-alkynylamine compound, 0.36mmol of alkynol, 3mL of 1, 2-dichloroethane, and PPh were added to a 10 mL reaction tube3AuCl 0.03mmol and AgOTf 0.03 mmol. The reaction was carried out at 25 ℃ for 4 hours to obtain the desired product of formula (ID) as a pale yellow oily liquid with an isolated yield of 80%.
Nuclear magnetic data of the product: 1H NMR (400MHz, CDCl)3):δ7.86-7.88(m,2H),7.53(d,J＝8.4Hz,2H),7.29-7.31(m,2H),7.20(d,J＝8.0Hz,2H),6.52(s,1H),3.89(s,3H),3.18(s,3H),3.07(d,J＝17.2Hz,1H),2.71-2.79(m,2H),2.45(d,J＝16.0Hz,1H),2.40(s,3H),1.77(s,3H),1.66(s,3H),1.32(s,3H)；13C NMR(100MHz,CDCl3):δ171.2,166.8,150.9,144.7,141.9,136.4,136.2,130.1,129.8,129.4,128.2,127.0,126.9,124.7,51.9,48.2,44.7,44.5,32.8,27.3,21.5,21.3,20.7。
High resolution mass spectral data: HRMS (ESI, m/z) calcd.for C27H32NO5S[M+H]+calc.:482.2001；found:482.1996。
Example 5:
synthesis of 1- (4-chlorophenyl) -5-methyl-5- (N-methyl-N-Ts carbamoylmethyl) -3- (2-propenylidene) cyclopentene (IE)
Under nitrogen atmosphere, 0.3mmol of 3-methyl-3-butene-1-alkynylamine compound, 0.36mmol of alkynol, 3mL of 1, 2-dichloroethane, and PPh were added to a 10 mL reaction tube3AuCl 0.03mmol and AgOTf 0.03 mmol. The reaction was carried out at 25 ℃ for 4 hours to give the desired product of formula (IE) as a pale yellow oily liquid in an isolated yield of 70%.
Nuclear magnetic data of the product: 1H NMR (400MHz, CDCl)3):δ7.75(d,J＝8.2Hz,2H),6.39-6.44(m,6H),6.60(s,1H),3.42(s,3H),3.23(d,J＝17.2Hz,1H),2.95(d,J＝17.2Hz,2H),2.64-2.68(m,4H),1.97(s,3H),1.87(s,3H),1.50(s,3H)；13C NMR(100MHz,CDCl3):δ171.2,151.0,144.6,136.3,136.1,135.7,132.6,129.7,129.1,128.7,128.2,126.9,123.5,48.2,44.7,44.2,32.8,27.1,21.5,21.2,20.6。
High resolution mass spectral data: HRMS (ESI, m/z) calcd.for C25H28ClNNaO3S[M+Na]+calc.:480.1376；found:480.1362。
Example 6:
synthesis of 1- (4-methylphenyl) -5-methyl-5- (N-methyl-N-Ts carbamoylmethyl) -3- (2-propenylidene) cyclopentene (IF)
Under nitrogen atmosphere, 0.3mmol of 3-methyl-3-butene-1-alkynylamine compound, 0.36mmol of alkynol, 3mL of 1, 2-dichloroethane, and PPh were added to a 10 mL reaction tube3AuCl 0.03mmol and AgOTf 0.03 mmol. The reaction was carried out at 25 ℃ for 4 hours to obtain the desired product of formula (IF), a pale yellow oily liquid, isolated in 75% yield.
Nuclear magnetic data of the product: 1H NMR (400MHz, CDCl)3):δ7.57-7.59(m,2H),7.16-7.22(m,4H),7.08(d,J＝7.9Hz,2H),6.38(s,1H),3.22(s,3H),3.07(d,J＝17.1Hz,1H),2.68-2.77(m,2H),2.46(d,J＝16.2Hz,1H),2.41(s,3H),2.35(s,3H),1.77(s,3H),1.66(s,3H),1.31(s,3H)；13C NMR(100MHz,CDCl3):δ171.6,152.5,144.5,136.6,136.5,136.4,134.2,129.7,128.8,128.0,127.4,127.1,122.4,48.3,44.9,44.3,32.9,26.9,21.5,21.2,21.1,20.6。
High resolution mass spectral data: HRMS (ESI, m/z) calcd.for C26H31NNaO3S[M+Na]+calc.:460.1922。
Example 7:
synthesis of 1- (4-methoxyphenyl) -5-methyl-5- (N-methyl-N-Ts carbamoylmethyl) -3- (2-propenylidene) cyclopentene (IG)
Under nitrogen atmosphere, 0.3mmol of 3-methyl-3-butene-1-alkynylamine compound, 0.36mmol of alkynol, 3mL of 1, 2-dichloroethane, and PPh were added to a 10 mL reaction tube3AuCl 0.03mmol and AgOTf 0.03 mmol. The reaction was carried out at 25 ℃ for 4 hours to give the desired product of formula (IG) as a pale yellow oily liquid in an isolated yield of 71%.
Nuclear magnetic data of the product: 1H NMR (400MHz, CDCl)3):δ7.55-7.57(m,2H),7.20-7.23(m,4H),6.79-6.82(m,2H),6.33(s,1H),3.80(s,3H),3.21(s,3H),3.06(d,J＝17.0Hz,1H),2.68-2.75(m,2H),2.40-2.47(m,4H),1.76(s,3H),1.65(s,3H),1.30(s,3H)；13C NMR(100MHz,CDCl3):δ171.6,158.7,152.2,144.5,136.5,136.4,129.8,129.7,128.6,127.6,127.1,122.1,113.5,55.2,48.3,44.9,44.3,32.9,26.9,21.5,21.1,20.6。
High resolution mass spectrometry data: HRMS (ESI, m/z) calcd.for C26H31NNaO4S[M+H]+calc.:476.1872；found:476.1858。
Example 8:
synthesis of 1- (9-phenanthryl) -5-methyl-5- (N-methyl-N-Ts carbamoylmethyl) -3- (2-propenylidene) cyclopentene (IH)
Under nitrogen atmosphere, 0.3mmol of 3-methyl-3-butene-1-alkynylamine compound, 0.36mmol of alkynol, 3mL of 1, 2-dichloroethane, and PPh were added to a 10 mL reaction tube3AuCl 0.03mmol and AgOTf 0.03 mmol. The reaction was carried out at 25 ℃ for 5 hours to obtain the desired product of formula (IH) as a pale yellow oily liquid with an isolated yield of 68%.
Nuclear magnetic data of the product: 1H NMR (400MHz, CDCl)3):δ8.74-8.78(m,2H),8.07(d,J＝8.1Hz,1H),7.84(d,J＝7.8Hz,1H),7.67-7.71(m,2H),7.59-7.64(m,2H),7.46(s,1H),7.04(d,J＝7.9Hz,2H),6.6(d,J＝8.2Hz,2H),6.38(s,1H),3.26(s,3H),2.99(d,J＝16.7Hz,1H),2.89(d,J＝17.2Hz,1H),2.63-2.74(m,2H),2.02(s,3H),1.79(s,3H),1.77(s,3H),1.07(s,3H)；13C NMR(100MHz,CDCl3):δ171.6,150.0,144.1,137.0,136.3,133.6,132.0,131.7,131.1,130.3,129.8,129.3,128.7,127.4,126.9,126.8,126.6,126.5,126.5,126.4,122.6,122.5,122.3,50.3,45.3,43.0,32.8,25.7,21.2,21.1,20.7。
High resolution mass spectrometry data: HRMS (ESI, m/z) calcd.for C33H34NO3S[M+H]+calc.:524.2259；found:524.2248。
Example 9:
synthesis of 1-N-butyl-5-methyl-5- (N-methyl-N-Ts carbamoylmethyl) -3- (2-propenylene) cyclopentene (II)
Under nitrogen atmosphere, 0.3mmol of 3-methyl-3-butene-1-alkynylamine compound, 0.36mmol of alkynol, 3mL of 1, 2-dichloroethane, and PPh were added to a 10 mL reaction tube3AuCl 0.03mmol and AgOTf 0.03 mmol. The reaction was carried out at 25 ℃ for 4 hours to obtain the desired product of formula (II), a pale yellow oily liquid, isolated in 65% yield.
Nuclear magnetic data of the product: 1H NMR (400MHz, CDCl)3):δ7.72(d,J＝7.72Hz,2H),7.31(d,J＝8.1Hz,2H),5.95(s,1H),3.25(s,3H),2.95(d,J＝16.6Hz,1H),2.47-2.54(m,2H),2.42(s,3H),2.28(d,J＝16.8Hz,1H),1.87-1.91(m,2H),1.69(s,3H),1.57(s,3H),1.44-1.48(m,2H),1.30-1.35(m,2H),1.05(s,3H),0.90(t,J＝7.3Hz,3H)；13C NMR(100MHz,CDCl3):δ171.8,154.8,144.7,136.7,129.9,127.4,127.2,124.0,118.9,48.2,44.6,42.8,33.0,30.2,26.7,25.6,22.8,21.6,21.0,20.5,14.0。
High resolution mass spectrometry data: HRMS (ESI, m/z) calcd.for C23H34NO3S[M+H]+calc.:404.2259；found:409.2253。
Example 10:
synthesis of 1-phenyl-5-methyl-5- (N-benzyl-N-Ts carbamoylmethyl) -3- (2-propenylene) cyclopentene (IJ)
Under nitrogen atmosphere, 0.3mmol of 3-methyl-3-butene-1-alkynylamine compound, 0.36mmol of alkynol, 3mL of 1, 2-dichloroethane, and PPh were added to a 10 mL reaction tube3AuCl 0.03mmol and AgOTf 0.03 mmol. The reaction was carried out at 25 ℃ for 6 hours to obtain the objective compound of formula (IJ) as a pale yellow oily liquid with an isolated yield of 83%.
Nuclear magnetic data of the product: 1H NMR (400MHz, CDCl)3):δ7.38-7.40(m,2H),7.24-7.30(m,8H),7.18-7.21(m,2H),7.13(d,J＝8.04Hz,2H),6.40(s,1H),5.08(s,2H),3.00(d,J＝17.1Hz,1H),2.72(d,J＝16.2Hz,1H),2.64(d,J＝17.1Hz,1H),2.47(d,J＝16.2Hz,1H),2.39(s,3H),1.79(s,3H),1.67(s,3H),1.28(s,3H)；13C NMR(100MHz,CDCl3):δ171.3,152.4,144.4,137.1,136.9,136.7,136.4,129.5,128.5,128.5,128.1,127.8,127.5,127.5,127.4,126.8,122.8,48.8,48.4,44.6,44.3,26.7,21.5,21.2,20.6。
High resolution mass spectrometry data: HRMS (ESI, m/z) calcd.for C31H34NO3S[M+H]+calc.:500.2259；found:500.2247。
Example 11:
synthesis of 1-phenyl-5-methyl-5- (N-cyclopropyl-N-Ts carbamoylmethyl) -3- (2-propenylene) cyclopentene (IK)
Under nitrogen atmosphere, 0.3mmol of 3-methyl-3-butene-1-alkynylamine compound, 0.36mmol of alkynol, 3mL of 1, 2-dichloroethane, and PPh were added to a 10 mL reaction tube3AuCl 0.03mmol、AgOTf 0.03mmol。The reaction was carried out at 25 ℃ for 6 hours to obtain the objective compound of formula (IK) as a pale yellow oily liquid with an isolated yield of 81%.
Nuclear magnetic data of the product: 1H NMR (400MHz, CDCl)3):δ7.69(d,J＝8.3Hz,2H),7.15-7.25(m,8H),6.34(s,1H),2.99(d,J＝16.3Hz,1H),2.63-2.69(m,2H),2.44-2.45(m,1H),2.30-2.36(m,4H),1.70(s,3H),1.58(s,3H),1.24(s,3H),0.85-0.87(m,2H),0.67-0.68(m,2H)；13C NMR(100MHz,CDCl3):δ173.7,152.2,144.2,137.0,136.7,136.3,129.3,128.6,128.1,128.0,127.4,126.9,122.9,48.7,45.4,44.0,28.2,26.8,21.5,21.1,20.6,9.8,9.8。
HRMS(ESI,m/z)calcd.for C27H32NO3S[M+H]+calc.:450.2103；found:450.2101。
Example 12:
synthesis of 1-phenyl-5-methyl-5- (N-methyl-N-Ms carbamoylmethyl) -3- (2-propenylene) cyclopentene (IL)
Under nitrogen atmosphere, 0.3mmol of 3-methyl-3-butene-1-alkynylamine compound, 0.36mmol of alkynol, 3mL of 1, 2-dichloroethane, and PPh were added to a 10 mL reaction tube3AuCl 0.03mmol and AgOTf 0.03 mmol. The reaction was carried out at 25 ℃ for 5 hours to obtain the objective compound of formula (IL) as a pale yellow oily liquid in an isolated yield of 76%.
Nuclear magnetic data of the product: 1H NMR (400MHz, CDCl)3):δ7.37-7.39(m,2H),7.30-7.34(m,2H),7.26-7.27(m,1H),6.50(s,1H),3.15(s,3H),3.07(s,3H),2.94(d,J＝16.8Hz,2H),2.74(d,J＝16.8Hz,1H),2.58(d,J＝16.0Hz,1H),1.82(s,3H),1.73(s,3H),1.49(s,3H)；13C NMR(100MHz,CDCl3):δ172.2,151.7,137.1,136.1,129.0,128.2,127.3,127.1,123.3,48.3,44.4,44.2,41.2,32.4,27.4,21.3,20.6。
High resolution mass spectrometry data: HRMS (ESI, m/z) calcd.for C19H26NO3S[M+H]+calc.:348.1633；found:348.1624。
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents and improvements made within the spirit and principle of the present invention are intended to be included within the scope of the present invention.
Claims (10)
1. A penta-substituted 3-alkenylene cyclopentene derivative is characterized by having a structure shown in a formula (I):
in the formula (I), the compound is shown in the specification,
R1is aryl, C1-C10 alkyl or C1-C10 cycloalkyl; r2Is alkylsulfonyl or arylsulfonyl; r3Is aryl or C1-C10 alkyl.
2. A method for synthesizing penta-substituted 3-alkenylene cyclopentene derivatives shown in formula (I) is characterized by comprising the following specific steps:
taking 3-methyl-3-butene-1-alkynylamine compounds and alkynol compounds as raw materials, adding an organic solvent and a catalyst in an atmosphere of protective gas, and catalytically synthesizing to obtain pentasubstituted 3-alkenylene cyclopentene derivatives shown in the formula (I);
the reaction process is shown as the formula (II):
in the formula (II), R1Is aryl, C1-C10 alkyl or C1-C10 cycloalkyl; r2Is alkylsulfonyl or arylsulfonyl; r3Is aryl or C1-C10 alkyl.
3. The method of claim 2, wherein R is R1Is methyl, ethyl, benzyl, cyclopropyl, cyclopentyl; r2P-toluenesulfonyl and methanesulfonyl; r3Is phenyl, 4-chlorophenyl, 4-bromophenyl,4-nitrophenyl, 4-esterylphenyl, 4-methylphenyl, 4-methoxyphenyl, 9-phenanthryl, n-butyl.
4. The method for synthesizing penta-substituted 3-alkenylene cyclopentene derivatives according to claim 2, wherein the catalyst is selected from PPh3AuNTf2、PPh3AuBF4、PPh3AuSbF6、PPh3AuOTf PPh3AuCl and PtCl2One or more of (a).
5. The method for synthesizing pentasubstituted 3-alkenylene cyclopentene derivatives according to claim 2, wherein the organic solvent is one or more selected from 1, 2-dichloroethane, dichloromethane, 1, 4-dioxane, acetonitrile, toluene, and chloroform.
6. The method for synthesizing pentasubstituted 3-alkenylcyclopentene derivatives according to claim 2, wherein the ratio of 3-methyl-3-butene-1-alkynylamine compounds: alkynol compounds: the molar ratio of the catalyst is 1: (1-2): (0.05-0.5).
7. The method for synthesizing penta-substituted 3-alkenylene cyclopentene derivatives according to claim 2, wherein the reaction temperature is 20-50 ℃.
8. The method for synthesizing penta-substituted 3-alkenylene cyclopentene derivatives according to claim 2, wherein the reaction time is 2-6 h.
9. The method as claimed in claim 2, wherein the protective gas is nitrogen or argon.
10. The use of penta-substituted 3-alkenylene cyclopentene derivatives according to claim 1 for the synthesis and modification of related natural products, active drug molecules.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2004143355A (en) * | 2002-10-28 | 2004-05-20 | Toyo Ink Mfg Co Ltd | Sensitizing dye for photoelectric conversion and its use |
| CN110678532A (en) * | 2017-05-22 | 2020-01-10 | 法国原子能源和替代能源委员会 | Organic photochromic dye and application thereof in dye-sensitized solar cell |
| CN111362895A (en) * | 2020-03-20 | 2020-07-03 | 临沂大学 | Synthesis method of naphthofuran derivative, naphthofuran derivative and application |
| CN111592544A (en) * | 2020-04-30 | 2020-08-28 | 华东师范大学 | Indoline aza eight-membered ring derivative and synthesis method thereof |
-
2021
- 2021-09-01 CN CN202111019540.0A patent/CN113582886A/en not_active Withdrawn
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2004143355A (en) * | 2002-10-28 | 2004-05-20 | Toyo Ink Mfg Co Ltd | Sensitizing dye for photoelectric conversion and its use |
| CN110678532A (en) * | 2017-05-22 | 2020-01-10 | 法国原子能源和替代能源委员会 | Organic photochromic dye and application thereof in dye-sensitized solar cell |
| CN111362895A (en) * | 2020-03-20 | 2020-07-03 | 临沂大学 | Synthesis method of naphthofuran derivative, naphthofuran derivative and application |
| CN111592544A (en) * | 2020-04-30 | 2020-08-28 | 华东师范大学 | Indoline aza eight-membered ring derivative and synthesis method thereof |
Non-Patent Citations (7)
| Title |
|---|
| CHANDRA M. R. VOLLA ET AL: "Palladium-Catalyzed Aerobic Domino Oxidative Carbocyclization-Alkynylation of Allenynes", 《ANGEW. CHEM. INT. ED.》 * |
| CHANDRA M.R.VOLLA ET AL: "Palladium-Catalyzed Oxidative Carbocyclization-Carbonylation of Allenynes and Enallenes", 《CHEM. EUR. J.》 * |
| ENRICO TAPAVICZA ET AL: "Tuning the photoreactivity of Z-hexatriene photoswitches by substituents-a non-adiabatic molecular dynamics study", 《PHYS. CHEM. CHEM. PHYS.》 * |
| TERESA BARTHOLOMEYZIK ET AL: "Kinetics and Mechanism of the Palladium-Catalyzed Oxidative Arylating Carbocyclization of Allenynes", 《J. AM. CHEM. SOC.》 * |
| TERESA BARTHOLOMEYZIK ET AL: "Palladium-Catalyzed Oxidative Arylating Carbocyclization of Allenynes: Control of Selectivity and Role of H2O", 《ANGEW. CHEM. INT. ED.》 * |
| YOUQIAN DENG ET AL: "Palladium-Catalyzed Oxidative Arylating Carbocyclization of Allenynes", 《ANGEW. CHEM. INT. ED.》 * |
| 王程宇: "金属催化的呋喃炔衍生物分子内环化及相关反应研究", 《中国博士学位论文全文数据库 工程科技Ⅰ辑》 * |
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