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2019 Volume 39 Issue 8
2019, 39(8): 2119-2130
doi: 10.6023/cjoc201904060
Abstract:
The development of efficient methods for the preparation of unnatural amino acids has long been an important goal since their widely application in synthetic and medicinal chemistry. The asymmetric α-functionalization of nucleophilic metalated azomethine ylides, which could be in situ-generated from readily-available aldimine esters, has been recogonized as a powerful strategy to synthesize unnatural amino acids. Over the past 20 years, tranistion metal-catalyzed asymmetric construction of unnatural amino acids using azomethine ylides have been extensively studied. In this review, the progress on metallated azomethine ylides invovled aymmetric transformation for the synthesis of unnatural amino acids is summarized according to eletrophilic reagents.
The development of efficient methods for the preparation of unnatural amino acids has long been an important goal since their widely application in synthetic and medicinal chemistry. The asymmetric α-functionalization of nucleophilic metalated azomethine ylides, which could be in situ-generated from readily-available aldimine esters, has been recogonized as a powerful strategy to synthesize unnatural amino acids. Over the past 20 years, tranistion metal-catalyzed asymmetric construction of unnatural amino acids using azomethine ylides have been extensively studied. In this review, the progress on metallated azomethine ylides invovled aymmetric transformation for the synthesis of unnatural amino acids is summarized according to eletrophilic reagents.
2019, 39(8): 2131-2138
doi: 10.6023/cjoc201904065
Abstract:
Synthesis of complex molecules via multicomponent reactions (MCRs) in a one-pot reaction manner has emerged as an important means to realize the value-added conversion of cheap and easily available renewable bio-based platform molecules. The diversity and multi-functionality of these biomass-derived molecules provide a fascinating platform for establishing MCRs, and in many cases, the developed MCRs would not be attained from less functionalized substrates. This review introduces some typical examples for the conversion of biomass-derived platform compounds to high value-added products through MCRs. It mainly summarizes the MCRs developed by using polyols, dicarboxylic acids, levulinic acid and furfural derivatives as one of the starting substrates. At the end of this review, a perspective of this direction is also given.
Synthesis of complex molecules via multicomponent reactions (MCRs) in a one-pot reaction manner has emerged as an important means to realize the value-added conversion of cheap and easily available renewable bio-based platform molecules. The diversity and multi-functionality of these biomass-derived molecules provide a fascinating platform for establishing MCRs, and in many cases, the developed MCRs would not be attained from less functionalized substrates. This review introduces some typical examples for the conversion of biomass-derived platform compounds to high value-added products through MCRs. It mainly summarizes the MCRs developed by using polyols, dicarboxylic acids, levulinic acid and furfural derivatives as one of the starting substrates. At the end of this review, a perspective of this direction is also given.
2019, 39(8): 2139-2147
doi: 10.6023/cjoc201903069
Abstract:
Scientists have found more and more sulfur compounds in food with the development of science and technology, high-precision analytical methods and equipment. In 2015, Flavor and Extract Manufactures Association of the United State published 2816 safe flavors, and there are more than 388 sulfur-containing compounds, accounting for more than 13%. The main smell of sulfur-containing flavors is food, especially the non-staple food and dishes. It is mainly used as food flavor, flower flavor and fruity flavor. Due to the increase of sulfur-containing perfume and flavors demand, its production scale is increasing, the research on synthesis methods is also deepening, and the green and efficient construction methods are also constantly reported. In this review, the recent progress in the construction of sulfide, thiol, thioester and polysulfide perfume & flavors is summarized.
Scientists have found more and more sulfur compounds in food with the development of science and technology, high-precision analytical methods and equipment. In 2015, Flavor and Extract Manufactures Association of the United State published 2816 safe flavors, and there are more than 388 sulfur-containing compounds, accounting for more than 13%. The main smell of sulfur-containing flavors is food, especially the non-staple food and dishes. It is mainly used as food flavor, flower flavor and fruity flavor. Due to the increase of sulfur-containing perfume and flavors demand, its production scale is increasing, the research on synthesis methods is also deepening, and the green and efficient construction methods are also constantly reported. In this review, the recent progress in the construction of sulfide, thiol, thioester and polysulfide perfume & flavors is summarized.
2019, 39(8): 2148-2156
doi: 10.6023/cjoc201903068
Abstract:
Eight membered cyclic ether compounds are common structural motifs in natural products and bioactive molecules. The efficient synthesis of eight membered ethers has attracted wide attention for organic chemists. Compared with five-to seven-membered cyclic ethers, the synthesis of eight membered cyclic ethers is more challenging. In this paper, the synthetic methods for eight membered cyclic ethers by transition metal catalysis, ring expansion, retro-Claisen rearrangement, ring-closing metathesis, intramolecular amide enol alkylation and organic catalyzed tandem cyclization are reviewed.
Eight membered cyclic ether compounds are common structural motifs in natural products and bioactive molecules. The efficient synthesis of eight membered ethers has attracted wide attention for organic chemists. Compared with five-to seven-membered cyclic ethers, the synthesis of eight membered cyclic ethers is more challenging. In this paper, the synthetic methods for eight membered cyclic ethers by transition metal catalysis, ring expansion, retro-Claisen rearrangement, ring-closing metathesis, intramolecular amide enol alkylation and organic catalyzed tandem cyclization are reviewed.
2019, 39(8): 2157-2165
doi: 10.6023/cjoc201906005
Abstract:
A phosphine-mediated Staudinger/Aza-Michael addition of azides with trifluoromethyl substituted α, β-unsaturated ketones was developed, giving hydroamination products in medium to good yields (up to 96%). The hydroamination products could be prepared on gram scale and a wide range of substrates are tolerated under the optimized reaction conditions (30 examples). 31P NMR experiments indicate that this reaction was initiated by Staudinger reaction of azide with phosphine.
A phosphine-mediated Staudinger/Aza-Michael addition of azides with trifluoromethyl substituted α, β-unsaturated ketones was developed, giving hydroamination products in medium to good yields (up to 96%). The hydroamination products could be prepared on gram scale and a wide range of substrates are tolerated under the optimized reaction conditions (30 examples). 31P NMR experiments indicate that this reaction was initiated by Staudinger reaction of azide with phosphine.
2019, 39(8): 2166-2174
doi: 10.6023/cjoc201905050
Abstract:
Carbazole and its derivatives are widely used in the field of medicine and photoelectric materials. A kind of stable cyclic hypervalent iodine reagents containing carbazole group was developed, which belong to benziodoxole compounds. In the presence of Cu(I) catalyst, these reagents reacted with aromatic substrates to give N-aryl carbazole derivatives. The reaction conditions are mild and suitable for a variety of electron-rich arenes. And a radical mechanism was proposed.
Carbazole and its derivatives are widely used in the field of medicine and photoelectric materials. A kind of stable cyclic hypervalent iodine reagents containing carbazole group was developed, which belong to benziodoxole compounds. In the presence of Cu(I) catalyst, these reagents reacted with aromatic substrates to give N-aryl carbazole derivatives. The reaction conditions are mild and suitable for a variety of electron-rich arenes. And a radical mechanism was proposed.
2019, 39(8): 2188-2195
doi: 10.6023/cjoc201904079
Abstract:
The asymmetric transfer hydrogenation represents one important class of reactions for the synthesis of optically active compounds. A chiral ammonia borane was generated in situ from an H2 release reaction between chiral phosphoric acid and ammonia borane, which could be regenerated by the assistance of water after the hydrogen transfer process and made this reaction catalytic. With this chiral ammonia borane, asymmetric transfer hydrogenations of β-enamine cyanides were realized to afford the desired products in 48%~98% yields with 61%~95% ee.
The asymmetric transfer hydrogenation represents one important class of reactions for the synthesis of optically active compounds. A chiral ammonia borane was generated in situ from an H2 release reaction between chiral phosphoric acid and ammonia borane, which could be regenerated by the assistance of water after the hydrogen transfer process and made this reaction catalytic. With this chiral ammonia borane, asymmetric transfer hydrogenations of β-enamine cyanides were realized to afford the desired products in 48%~98% yields with 61%~95% ee.
2019, 39(8): 2196-2202
doi: 10.6023/cjoc201901040
Abstract:
The phosphine-catalyzed[3+2] annulation of γ-methyl allenoates with 2-arylidene-1H-indene-1, 3(2H)-diones is reported. In the reaction, a series of highly functionalized spiro[4.4]dec-6-ene skeletons were obtained in moderate to good yields and high diastereoselectivities. It should be noted that the perfect α-regioselective annulation adducts were obtained with simple PPh3 catalyst.
The phosphine-catalyzed[3+2] annulation of γ-methyl allenoates with 2-arylidene-1H-indene-1, 3(2H)-diones is reported. In the reaction, a series of highly functionalized spiro[4.4]dec-6-ene skeletons were obtained in moderate to good yields and high diastereoselectivities. It should be noted that the perfect α-regioselective annulation adducts were obtained with simple PPh3 catalyst.
2019, 39(8): 2211-2217
doi: 10.6023/cjoc201903065
Abstract:
A novel palladium(0)-catalyzed dearomative spirocyclization reaction of bromophenols has been developed for building a series of spirocyclic architectures containing a quaternary carbon center via[2+2+1] strategy. This method employs inexpensive bromophenols and easily accessible alkynes. It exhibits a broad substrate scope in good yields. Notably, this transformation can be realized with high regioselectivity (>19:1 rr) when using unsymmetrical alkynes, which greatly expands the research scope of phenol dearomatization.
A novel palladium(0)-catalyzed dearomative spirocyclization reaction of bromophenols has been developed for building a series of spirocyclic architectures containing a quaternary carbon center via[2+2+1] strategy. This method employs inexpensive bromophenols and easily accessible alkynes. It exhibits a broad substrate scope in good yields. Notably, this transformation can be realized with high regioselectivity (>19:1 rr) when using unsymmetrical alkynes, which greatly expands the research scope of phenol dearomatization.
2019, 39(8): 2243-2250
doi: 10.6023/cjoc201904040
Abstract:
Treatment of PhSbCl2 with 2 equiv. of (2, 6-Cl2C6H3)(2-LiC6H4)NLi, which was generated in situ by the interaction of (2, 6-Cl2C6H3)(2-BrC6H4)NH with 2 equiv. of BunLi, followed by quenching with water, afforded the diamine-stibine compound ((o-(N-(2, 6-Cl2C6H3)NH)C6H4)2SbPh (denoted as H2(dcpN2Sb)). H2(dcpN2Sb) undergoes amine-elimination reaction with[Fe(N(SiMe3)2)2]2 (0.5 euiqv.) to afford an iron(Ⅱ) complex[(κ3-N, N, Sb-dcpN2Sb)Fe(THF)] (1) bearing an unique tridentate bisamido-stibine ligand. Solution magnetic susceptibility measurements (μeff=4.7(2) μB in C6D6) reveal a high spin (S=2) electronic structure for 1. Complex 1 represents the first high-spin iron(Ⅱ) complex with organic stibine ligation, and features a long Fe-Sb bond distance of 0.2792(1) nm. Density functional theory (DFT) calculations indicate weak σ interaction betwen the high-spin iron(Ⅱ) center and the antimony atom due to ineffective orbital overlap. Complex 1 can react with organic azides RN3 to furnish the high-spin (S=2) iron(Ⅱ) complexes that bear tridentate bisamido-stibonium imine ligands[(κ3-N, N, N-dcpN2SbNR)Fe(py)] (R=dcp (2, 6-Cl2C6H3), 2; R=Dipp (2, 6-iPr2C6H3), 3). These compexes are among the rare metal complexes with stibonium imine ligation. The average Sb-N distance of 0.194 nm in the imine moieties is found comparable to those of the Sb-N bonds in the reported stibonium imine compounds Mes3SbNCOCl3 (0.199 nm) and 2-MeC6H4)3SbNSO2CF3 (0.196 nm). The reactions of 1 with diazo compounds (R1R2)CN2 afford the high-spin iron(Ⅱ) complexes featuring tridentate bisamido-stibonium ylide ligands[(κ3-N, N, C-dcpN2SbCR1, R2)Fe(PMe3)] (R1=H, R2=CO2But, 4; R1=Ph, R2=CO2Et, 5). The average Sb-C distance of 0.206 nm in the ylide moieties is found comparable to those of the Sb-C bonds in the reported stibonium ylide compounds (around 0.20 nm). H2(dcpN2Sb) and 1~5 have been characterized by elemental analysis, 1H NMR, solution magnetic susceptibility measurements and single-crystal X-ray diffraction studies.
Treatment of PhSbCl2 with 2 equiv. of (2, 6-Cl2C6H3)(2-LiC6H4)NLi, which was generated in situ by the interaction of (2, 6-Cl2C6H3)(2-BrC6H4)NH with 2 equiv. of BunLi, followed by quenching with water, afforded the diamine-stibine compound ((o-(N-(2, 6-Cl2C6H3)NH)C6H4)2SbPh (denoted as H2(dcpN2Sb)). H2(dcpN2Sb) undergoes amine-elimination reaction with[Fe(N(SiMe3)2)2]2 (0.5 euiqv.) to afford an iron(Ⅱ) complex[(κ3-N, N, Sb-dcpN2Sb)Fe(THF)] (1) bearing an unique tridentate bisamido-stibine ligand. Solution magnetic susceptibility measurements (μeff=4.7(2) μB in C6D6) reveal a high spin (S=2) electronic structure for 1. Complex 1 represents the first high-spin iron(Ⅱ) complex with organic stibine ligation, and features a long Fe-Sb bond distance of 0.2792(1) nm. Density functional theory (DFT) calculations indicate weak σ interaction betwen the high-spin iron(Ⅱ) center and the antimony atom due to ineffective orbital overlap. Complex 1 can react with organic azides RN3 to furnish the high-spin (S=2) iron(Ⅱ) complexes that bear tridentate bisamido-stibonium imine ligands[(κ3-N, N, N-dcpN2SbNR)Fe(py)] (R=dcp (2, 6-Cl2C6H3), 2; R=Dipp (2, 6-iPr2C6H3), 3). These compexes are among the rare metal complexes with stibonium imine ligation. The average Sb-N distance of 0.194 nm in the imine moieties is found comparable to those of the Sb-N bonds in the reported stibonium imine compounds Mes3SbNCOCl3 (0.199 nm) and 2-MeC6H4)3SbNSO2CF3 (0.196 nm). The reactions of 1 with diazo compounds (R1R2)CN2 afford the high-spin iron(Ⅱ) complexes featuring tridentate bisamido-stibonium ylide ligands[(κ3-N, N, C-dcpN2SbCR1, R2)Fe(PMe3)] (R1=H, R2=CO2But, 4; R1=Ph, R2=CO2Et, 5). The average Sb-C distance of 0.206 nm in the ylide moieties is found comparable to those of the Sb-C bonds in the reported stibonium ylide compounds (around 0.20 nm). H2(dcpN2Sb) and 1~5 have been characterized by elemental analysis, 1H NMR, solution magnetic susceptibility measurements and single-crystal X-ray diffraction studies.
2019, 39(8): 2251-2256
doi: 10.6023/cjoc201904017
Abstract:
Rauhut-Currier (RC) reaction is an effective atom-economic method to construct C-C bond. However, the application of this reaction is limited by the lack of selectivity. Herein, an efficient intermolecular cross Rauhut-Currier reaction between chalcones and acrylates in the presence of the tributylphosphine catalyst was developed, the reactions were carried out in mild conditions, and performed well with a series of substrates, delivering the desired products with acceptable to good yields.
Rauhut-Currier (RC) reaction is an effective atom-economic method to construct C-C bond. However, the application of this reaction is limited by the lack of selectivity. Herein, an efficient intermolecular cross Rauhut-Currier reaction between chalcones and acrylates in the presence of the tributylphosphine catalyst was developed, the reactions were carried out in mild conditions, and performed well with a series of substrates, delivering the desired products with acceptable to good yields.
2019, 39(8): 2264-2269
doi: 10.6023/cjoc201903047
Abstract:
Transition metal catalyzed codimeriaztion of alkenes is an important carbon-carbon bond forming reaction. This efficient reaction has the properties of easily available of starting materials, atomic economy, and good prospects for industrial application, and has been received in-depth and intensive study during the past decades. In this paper, we have systematically studied the ruthenium catalyzed codimerization of N-acetyl enamides with alkenes and found that the ruthenium hydride complex RuHCl(CO)(PCy3)2 is highly efficient catalyst for the codimerization of N-acetyl α-arylethenamines 1 with vinylarenes 4, providing the head-to-tail hetero-codimerized products, poly-substituted N-acetyl enamides 5 with high chemo-and regio-selectivity and up to 99% yield. According to the results and the observed phenomena of the codimerization reaction, we proposed a reaction mechanism that the vinylarenes 4 was firstly inserted into the Ru-H bond of the activated ruthenium hydride intermediate to form an allylic metal-intermediate and then codimerized with N-acetyl α-arylethenamines 1 to generate the hetero-codimerized poly-substituted N-acetyl enamides 5. With this proposed reaction mechanism the reaction results and the observed phenomena can be rational explanation.
Transition metal catalyzed codimeriaztion of alkenes is an important carbon-carbon bond forming reaction. This efficient reaction has the properties of easily available of starting materials, atomic economy, and good prospects for industrial application, and has been received in-depth and intensive study during the past decades. In this paper, we have systematically studied the ruthenium catalyzed codimerization of N-acetyl enamides with alkenes and found that the ruthenium hydride complex RuHCl(CO)(PCy3)2 is highly efficient catalyst for the codimerization of N-acetyl α-arylethenamines 1 with vinylarenes 4, providing the head-to-tail hetero-codimerized products, poly-substituted N-acetyl enamides 5 with high chemo-and regio-selectivity and up to 99% yield. According to the results and the observed phenomena of the codimerization reaction, we proposed a reaction mechanism that the vinylarenes 4 was firstly inserted into the Ru-H bond of the activated ruthenium hydride intermediate to form an allylic metal-intermediate and then codimerized with N-acetyl α-arylethenamines 1 to generate the hetero-codimerized poly-substituted N-acetyl enamides 5. With this proposed reaction mechanism the reaction results and the observed phenomena can be rational explanation.
2019, 39(8): 2270-2276
doi: 10.6023/cjoc201902029
Abstract:
An efficient and one-pot method for the preparation of 2-((2-aminobenzoyl)amino)benzoic acid derivatives has been reported. Twenty 2-((2-aminobenzoyl)amino)benzoic acid derivatives were prepared with 84%~99% yields and nine compounds are new compounds. The effects of electron effect and steric hindrance on the reaction were discussed. It provides an operationally simple, environmentally friendly, high yield and good substrate universality method for the synthesis of 2-(2-aminobenzamide)benzoic acid derivatives. Furthermore, macrolide 4 and quinazolinone 5 can be synthesized from 2-((2-ami-nobenzoyl)amino)benzoic acid (3a) in one-step over 92% yields.
An efficient and one-pot method for the preparation of 2-((2-aminobenzoyl)amino)benzoic acid derivatives has been reported. Twenty 2-((2-aminobenzoyl)amino)benzoic acid derivatives were prepared with 84%~99% yields and nine compounds are new compounds. The effects of electron effect and steric hindrance on the reaction were discussed. It provides an operationally simple, environmentally friendly, high yield and good substrate universality method for the synthesis of 2-(2-aminobenzamide)benzoic acid derivatives. Furthermore, macrolide 4 and quinazolinone 5 can be synthesized from 2-((2-ami-nobenzoyl)amino)benzoic acid (3a) in one-step over 92% yields.
2019, 39(8): 2277-2286
doi: 10.6023/cjoc201903042
Abstract:
1-Phosphafulvenes are unique in their cycloaddition reactions, which act as 2π, 4π, and 6π systems and provide versatile and powerful approaches to various polycyclic systems. The reaction of 1-phosphafulvene with 1, 4-benzoquinone and N-phenylmaleimide upon heating provided phosphapolycyclic rings in moderate to good yields. The possible mechanism included an oxidative addition of 1-phosphafulvene with 1, 4-benzoquinone and successive Diels-Alder reactions with N-phenylmaleimide. The exocyclic C=C bond of 1-phosphafulvene is cruial to this reaction.
1-Phosphafulvenes are unique in their cycloaddition reactions, which act as 2π, 4π, and 6π systems and provide versatile and powerful approaches to various polycyclic systems. The reaction of 1-phosphafulvene with 1, 4-benzoquinone and N-phenylmaleimide upon heating provided phosphapolycyclic rings in moderate to good yields. The possible mechanism included an oxidative addition of 1-phosphafulvene with 1, 4-benzoquinone and successive Diels-Alder reactions with N-phenylmaleimide. The exocyclic C=C bond of 1-phosphafulvene is cruial to this reaction.
2019, 39(8): 2287-2294
doi: 10.6023/cjoc201903023
Abstract:
A series of 1, 3, 4-thiadiazolo[3, 2-a]pyrimidinone mesoionic derivatives were designed and synthesized with triflumezopyrim as the leading compound, and their structures were characterized by 1H NMR, 13C NMR, 19F NMR and HRMS. The preliminary biological activities indicated that the target compounds showed certain insecticidal activities at 100 μg/mL, of which the lethality rates of 2-((4-chlorobenzyl)thio)-8-((2-chlorothiazol-5-yl)methyl)-5-oxo-6-(3-(trifluoromethyl)phen-yl)-5H-[1, 3, 4]-thiadiazolo[3, 2-a]pyrimidin-8-ium-7-olate (8b) and 2-(((2-chlorothiazol-5-yl)methyl)thio)-8-((2-chlorothiazol-5-yl)methyl)-5-oxo-6-(3-(trifluoromethyl)phenyl)-5H-[1, 3, 4]thiadiazolo-[3, 2-a]pyrimidin-8-ium-7-olate (8d) against white-backed planthopper (WBPH) were 70%. Some compounds showed good antibacterial activities against Xanthomonas oryzae pv. oryzae (Xoo), Xanthomonas oryzae pv. oryzicola (Xoc) and Xanthomonas citri pv. citri (Xcc) at 50 μg/mL, and the inhi-bitory rates of 2-((2-(trifluoromethyl)benzyl)thio)-8-((2-chlorothiazol-5-yl)methyl)-5-oxo-6-(3-(trifluoromethyl)phenyl)-5H-[1, 3, 4]thiadiazolo[3, 2-a]pyrimidin-8-ium-7-olate (8h) to Xoo and Xoc were 70.91% and 53.34%, respectively, which were better than thiodiazole copper (47.76% and 23.25%) and bismerthiazol (66.97% and 17.24%). The inhibition rate of 2-((3-(tri-fluoromethyl)benzyl)thio)-8-((2-chlorothiazol-5-yl)methyl)-5-oxo-6-(3-(trifluoromethyl)phenyl)-5H-[1, 3, 4]thiadiazolo[3, 2-a]-pyrimidin-8-ium-7-olate (8e) to Xcc was 68.97%, which was better than thiediazole copper (35.85%) and bismerthiazol (37.53%)
A series of 1, 3, 4-thiadiazolo[3, 2-a]pyrimidinone mesoionic derivatives were designed and synthesized with triflumezopyrim as the leading compound, and their structures were characterized by 1H NMR, 13C NMR, 19F NMR and HRMS. The preliminary biological activities indicated that the target compounds showed certain insecticidal activities at 100 μg/mL, of which the lethality rates of 2-((4-chlorobenzyl)thio)-8-((2-chlorothiazol-5-yl)methyl)-5-oxo-6-(3-(trifluoromethyl)phen-yl)-5H-[1, 3, 4]-thiadiazolo[3, 2-a]pyrimidin-8-ium-7-olate (8b) and 2-(((2-chlorothiazol-5-yl)methyl)thio)-8-((2-chlorothiazol-5-yl)methyl)-5-oxo-6-(3-(trifluoromethyl)phenyl)-5H-[1, 3, 4]thiadiazolo-[3, 2-a]pyrimidin-8-ium-7-olate (8d) against white-backed planthopper (WBPH) were 70%. Some compounds showed good antibacterial activities against Xanthomonas oryzae pv. oryzae (Xoo), Xanthomonas oryzae pv. oryzicola (Xoc) and Xanthomonas citri pv. citri (Xcc) at 50 μg/mL, and the inhi-bitory rates of 2-((2-(trifluoromethyl)benzyl)thio)-8-((2-chlorothiazol-5-yl)methyl)-5-oxo-6-(3-(trifluoromethyl)phenyl)-5H-[1, 3, 4]thiadiazolo[3, 2-a]pyrimidin-8-ium-7-olate (8h) to Xoo and Xoc were 70.91% and 53.34%, respectively, which were better than thiodiazole copper (47.76% and 23.25%) and bismerthiazol (66.97% and 17.24%). The inhibition rate of 2-((3-(tri-fluoromethyl)benzyl)thio)-8-((2-chlorothiazol-5-yl)methyl)-5-oxo-6-(3-(trifluoromethyl)phenyl)-5H-[1, 3, 4]thiadiazolo[3, 2-a]-pyrimidin-8-ium-7-olate (8e) to Xcc was 68.97%, which was better than thiediazole copper (35.85%) and bismerthiazol (37.53%)
2019, 39(8): 2295-2302
doi: 10.6023/cjoc201903064
Abstract:
Pyruvate dehydrogenase multienzyme complex (PDHc) is a key enzyme linking glycolysis and the tricarboxylic acid cycle. Currently, there is no fungicide targeting pyruvate decarboxylase (PDHc-E1), the purpose of this study was to obtain compounds with bactericidal activity by designing inhibitors against PDHc-E1. On the basis of lead compound L, fourteen novel aminopyrimidine derivatives I were designed and synthesized by the condensation reaction of hydrazine and aldehydes as potential PDHc-E1 inhibitors. The most effective 5-((2-(4-bromophenyl)hydrazono)methyl)-2-methylpyridin-4-amine (I-6) with good E. coli PDHc-E1 enzyme inhibitory activity (IC50=26.45 μmol/L) exhibited most powerful inhibitory potency against Cercospora arachidicola Hori (EC50 14.11 μg/mL) and Physalospora piricola Nose (EC50 0.64 μg/mL). Therefore it could obtain the compound with antifungal activity against microorganism PDHc-E1 enzyme by modifying the bridged linkage in lead structure 2-methyl-4-amino-pyrimidine derivatives L.
Pyruvate dehydrogenase multienzyme complex (PDHc) is a key enzyme linking glycolysis and the tricarboxylic acid cycle. Currently, there is no fungicide targeting pyruvate decarboxylase (PDHc-E1), the purpose of this study was to obtain compounds with bactericidal activity by designing inhibitors against PDHc-E1. On the basis of lead compound L, fourteen novel aminopyrimidine derivatives I were designed and synthesized by the condensation reaction of hydrazine and aldehydes as potential PDHc-E1 inhibitors. The most effective 5-((2-(4-bromophenyl)hydrazono)methyl)-2-methylpyridin-4-amine (I-6) with good E. coli PDHc-E1 enzyme inhibitory activity (IC50=26.45 μmol/L) exhibited most powerful inhibitory potency against Cercospora arachidicola Hori (EC50 14.11 μg/mL) and Physalospora piricola Nose (EC50 0.64 μg/mL). Therefore it could obtain the compound with antifungal activity against microorganism PDHc-E1 enzyme by modifying the bridged linkage in lead structure 2-methyl-4-amino-pyrimidine derivatives L.
2019, 39(8): 2303-2310
doi: 10.6023/cjoc201901043
Abstract:
Acetohydroxyacid synthase (AHAS) was one of important herbicidal targets. However, the issue of weed resistance to commercial AHAS inhibitors has become one of the largest obstacles for their application. Therefore, there is a high demand to design new anti-resistance AHAS inhibitors. Herein, based on the reported low resistance AHAS inhibitors, a series of pyrimidyl-salicylates with "double oxygen bridge" utilized the "conformation flexibility analysis" strategy were designed. All the synthesized compounds were characterized by 1H NMR, 13C NMR and HRMS. The bioactivity results showed that most of the derivatives displayed good inhibitory activities against P197L mutant. Especially, 2-((4, 6-dimethoxypyrimidin-2-yl)oxy)-6-(2-fluoro-4-nitrophenoxy)-4-methylbenzoic acid (6l) was identified as the most potent anti-resistance AHAS inhibitor. In addition, some compounds showed good weed control for resistant Descurainia sophia (P197L AHAS). Most importantly, 2-((4, 6-dimethoxypyrimidin-2-yl)oxy)-6-(2-fluorophenoxy)-4-methylbenzoic acid (6b) showed 80% herbicidal activities against sensitive and resistant Descurainia sophia at the dosage of 150 g ai/ha. These results indicated that this type of compounds worth of the further investigation.
Acetohydroxyacid synthase (AHAS) was one of important herbicidal targets. However, the issue of weed resistance to commercial AHAS inhibitors has become one of the largest obstacles for their application. Therefore, there is a high demand to design new anti-resistance AHAS inhibitors. Herein, based on the reported low resistance AHAS inhibitors, a series of pyrimidyl-salicylates with "double oxygen bridge" utilized the "conformation flexibility analysis" strategy were designed. All the synthesized compounds were characterized by 1H NMR, 13C NMR and HRMS. The bioactivity results showed that most of the derivatives displayed good inhibitory activities against P197L mutant. Especially, 2-((4, 6-dimethoxypyrimidin-2-yl)oxy)-6-(2-fluoro-4-nitrophenoxy)-4-methylbenzoic acid (6l) was identified as the most potent anti-resistance AHAS inhibitor. In addition, some compounds showed good weed control for resistant Descurainia sophia (P197L AHAS). Most importantly, 2-((4, 6-dimethoxypyrimidin-2-yl)oxy)-6-(2-fluorophenoxy)-4-methylbenzoic acid (6b) showed 80% herbicidal activities against sensitive and resistant Descurainia sophia at the dosage of 150 g ai/ha. These results indicated that this type of compounds worth of the further investigation.
2019, 39(8): 2175-2182
doi: 10.6023/cjoc201904082
Abstract:
A 1, 4-diazabicyclo[2.2.2]octane (DABCO)-catalyzed[4+2] annulation reaction between 2-alkylidenebenzothio phene-3(2H)-ones and allenoate has been developed. The substrate scope includes both electron-withdrawing and electron-donating groups on the benzothiophene moiety. This method can be carried out under mild conditions and gives a wide range of highly functionalized benzothiophene-fused γ-pyran derivatives in good yields with moderate selectivity.
A 1, 4-diazabicyclo[2.2.2]octane (DABCO)-catalyzed[4+2] annulation reaction between 2-alkylidenebenzothio phene-3(2H)-ones and allenoate has been developed. The substrate scope includes both electron-withdrawing and electron-donating groups on the benzothiophene moiety. This method can be carried out under mild conditions and gives a wide range of highly functionalized benzothiophene-fused γ-pyran derivatives in good yields with moderate selectivity.
2019, 39(8): 2183-2187
doi: 10.6023/cjoc201905001
Abstract:
Alkenylphosphoryl compounds could quickly replace two phosphine ligands in Pd(PEt3)4 at room temperature to produce the corresponding palladium complexes 3a~3e in high yields. Similar nickel and platinium complexes 3f and 3g were also synthesized by the reaction. Complex 3e could react with HOAc to release alkenylphosphoryl compounds gradually. By further addition of 2 equiv. of PEt3, the reaction could take place completely, generating a phosphoniun 4 as a precipitation. Being similar to Pd(PEt3)4, 3d could also undergo hydropalladation with the combination of phenylacetylene and (EtO)2P(O)H, forming the expected vinyl-Pd-phosphoryl complex, but with a slower reaction rate. The result indicated that alkenylphosphoryl compounds generated from the palladium-catalyzed hydrophosphorylation of alkynes with H-phosphonates might play a negative role in the hydropalladation step of the catalytic cycle. Complexes 3a~3g and phosphonium 4 were charaterized by NMR analysis. The structures of 3a and 4 were also confirmed by X-ray technology.
Alkenylphosphoryl compounds could quickly replace two phosphine ligands in Pd(PEt3)4 at room temperature to produce the corresponding palladium complexes 3a~3e in high yields. Similar nickel and platinium complexes 3f and 3g were also synthesized by the reaction. Complex 3e could react with HOAc to release alkenylphosphoryl compounds gradually. By further addition of 2 equiv. of PEt3, the reaction could take place completely, generating a phosphoniun 4 as a precipitation. Being similar to Pd(PEt3)4, 3d could also undergo hydropalladation with the combination of phenylacetylene and (EtO)2P(O)H, forming the expected vinyl-Pd-phosphoryl complex, but with a slower reaction rate. The result indicated that alkenylphosphoryl compounds generated from the palladium-catalyzed hydrophosphorylation of alkynes with H-phosphonates might play a negative role in the hydropalladation step of the catalytic cycle. Complexes 3a~3g and phosphonium 4 were charaterized by NMR analysis. The structures of 3a and 4 were also confirmed by X-ray technology.
2019, 39(8): 2203-2210
doi: 10.6023/cjoc201703070
Abstract:
A chiral bifunctional squaramide catalyzed enantioselective formal[3+3] annulation of 4-hydroxy-2H-pyrano[2', 3':4, 5]pyrano[2, 3-c]pyrazole-2, 5(7H)-diones and (E)-2-nitroallyl acetates has been developed, which provides an efficient approach to stereocontrolled construction of fused polycyclic 3, 4-dihydropyrano[4, 3-b]pyran-5(2H)-one scaffold. Under the catalysis of a bifunctional squaramide derived from (1R, 2R)-1, 2-diphenylethane-1, 2-diamine, a wide range of novel fused polycyclic 3, 4-dihydropyrano[4, 3-b]pyran-5(2H)-one derivatives with two adjacent stereogenic centers are obtained in acceptable yields with high anti-selectivity and moderate to excellent enantioselectivity. Representative transformation of the annulation product to other synthetic valuable compound is achieved without any loss of stereochemical integrity.
A chiral bifunctional squaramide catalyzed enantioselective formal[3+3] annulation of 4-hydroxy-2H-pyrano[2', 3':4, 5]pyrano[2, 3-c]pyrazole-2, 5(7H)-diones and (E)-2-nitroallyl acetates has been developed, which provides an efficient approach to stereocontrolled construction of fused polycyclic 3, 4-dihydropyrano[4, 3-b]pyran-5(2H)-one scaffold. Under the catalysis of a bifunctional squaramide derived from (1R, 2R)-1, 2-diphenylethane-1, 2-diamine, a wide range of novel fused polycyclic 3, 4-dihydropyrano[4, 3-b]pyran-5(2H)-one derivatives with two adjacent stereogenic centers are obtained in acceptable yields with high anti-selectivity and moderate to excellent enantioselectivity. Representative transformation of the annulation product to other synthetic valuable compound is achieved without any loss of stereochemical integrity.
2019, 39(8): 2257-2263
doi: 10.6023/cjoc201903076
Abstract:
The chemistry of frustrated Lewis pairs (FLPs) is among the challenging frontiers of synthetic chemistry, which provides a powerful approach for metal-free catalytic hyrogenations and Piers-type hydrosilylations. In recent years, a significant progress has been made in this field. However, the deveopment of asymmetric reactions is still sluggish. The lacks of highly effective and enantioselective chiral FLP catalysts represent the key issue. C2-symmetric 1, 1'-spirobiindane is one privileged framework in chiral ligands and catalysts. On the basis of chiral binaphthyl diene-derived frustrated Lewis pairs (FLPs) developed by our group, in this work, we designed and synthesized a novel class of chiral spiro dienes, which could further react with Piers' borane via the hydroboration reaction to generate chiral boranes in situ. With the combination of chiral borane and tri-tert-butylphosphine as an FLP catalyst, an asymmetric Piers-type hydrosilylation of simple ketones was successfully realized to give the desired secondary alcohols with up to 90% ee.
The chemistry of frustrated Lewis pairs (FLPs) is among the challenging frontiers of synthetic chemistry, which provides a powerful approach for metal-free catalytic hyrogenations and Piers-type hydrosilylations. In recent years, a significant progress has been made in this field. However, the deveopment of asymmetric reactions is still sluggish. The lacks of highly effective and enantioselective chiral FLP catalysts represent the key issue. C2-symmetric 1, 1'-spirobiindane is one privileged framework in chiral ligands and catalysts. On the basis of chiral binaphthyl diene-derived frustrated Lewis pairs (FLPs) developed by our group, in this work, we designed and synthesized a novel class of chiral spiro dienes, which could further react with Piers' borane via the hydroboration reaction to generate chiral boranes in situ. With the combination of chiral borane and tri-tert-butylphosphine as an FLP catalyst, an asymmetric Piers-type hydrosilylation of simple ketones was successfully realized to give the desired secondary alcohols with up to 90% ee.
2019, 39(8): 2218-2225
doi: 10.6023/cjoc201903061
Abstract:
The formal[6+2] cycloaddition reaction of α'-methylene-2-cyclopentenones and 2-alkylidene-1, 3-indanediones was developed under the catalysis of tricyclohexyl phosphine, proceeding in a remote γ-regioselective Rauhut-Currier-type reaction followed by a β'-regioselective intramolecular Michael addition process. An array of fused bicyclic frameworks incorperating a spiro-1, 3-indanedione motif were produced in fair to good yields of 48%~76% with excellent diastereoseletivity (generally>19:1 dr). This protocol expands the reaction mode of traditional Rauhut-Currier reaction, which might find further application in organic synthesis.
The formal[6+2] cycloaddition reaction of α'-methylene-2-cyclopentenones and 2-alkylidene-1, 3-indanediones was developed under the catalysis of tricyclohexyl phosphine, proceeding in a remote γ-regioselective Rauhut-Currier-type reaction followed by a β'-regioselective intramolecular Michael addition process. An array of fused bicyclic frameworks incorperating a spiro-1, 3-indanedione motif were produced in fair to good yields of 48%~76% with excellent diastereoseletivity (generally>19:1 dr). This protocol expands the reaction mode of traditional Rauhut-Currier reaction, which might find further application in organic synthesis.
2019, 39(8): 2226-2234
doi: 10.6023/cjoc201903040
Abstract:
A novel method of copper-catalyzed cyclization of 1-aryl-1-cycloalcohols and 1, 3-dicarbonyl compounds has been developed, affording various cycloalkane-fused dihydrofurans in moderate to excellent yields. This transformation proceeds under mild conditions and with a good tolerance of functional groups. The mechanistic investigation revealed that the reaction involved radical intermediates.
A novel method of copper-catalyzed cyclization of 1-aryl-1-cycloalcohols and 1, 3-dicarbonyl compounds has been developed, affording various cycloalkane-fused dihydrofurans in moderate to excellent yields. This transformation proceeds under mild conditions and with a good tolerance of functional groups. The mechanistic investigation revealed that the reaction involved radical intermediates.
2019, 39(8): 2235-2242
doi: 10.6023/cjoc201904041
Abstract:
In this work, a phosphine-catalyzed[4+1] annulation between salicyl imines and maleimides has been successfully developed, which readily produces spiro[benzofuran-2, 3'-pyrrolidine] derivatives in 44%~99% yields. The annulation products were obtained as a pair of syn-and anti-isomers with dr 1.6:1~5:1. The syn-and anti-isomers can be readily separated by column chromatography on silica gel. Thus, this reaction constitutes a simple and efficient method for the synthesis of spiro[benzofuran-2, 3'-pyrrolidines]. Presumably, the reaction is initiated by in situ generated non-allylic P-ylide from maleimide and PPh3, and proceeds through a cascade sequence of nucleophilic addition/intramolecular SN2-like substitution. It accordingly represents a new example of the phosphine-catalyzed[4+1] annulation via in situ generated non-allylic P-ylides.
In this work, a phosphine-catalyzed[4+1] annulation between salicyl imines and maleimides has been successfully developed, which readily produces spiro[benzofuran-2, 3'-pyrrolidine] derivatives in 44%~99% yields. The annulation products were obtained as a pair of syn-and anti-isomers with dr 1.6:1~5:1. The syn-and anti-isomers can be readily separated by column chromatography on silica gel. Thus, this reaction constitutes a simple and efficient method for the synthesis of spiro[benzofuran-2, 3'-pyrrolidines]. Presumably, the reaction is initiated by in situ generated non-allylic P-ylide from maleimide and PPh3, and proceeds through a cascade sequence of nucleophilic addition/intramolecular SN2-like substitution. It accordingly represents a new example of the phosphine-catalyzed[4+1] annulation via in situ generated non-allylic P-ylides.
2019, 39(8): 2311-2316
doi: 10.6023/cjoc201905007
Abstract:
Penta-coordinated phosphoranes (ab2) with a five-member cycle and three ligands would simultaneously exchange with themselves under base catalysis to form three different penta-oxy phosphoranes with all the combinatorial ligands referred as a3, b3, and a2b. If we consider a3 and b3 as parents, the products obtained from exchange, namely a2b and ab2, could be regarded as the offspring of the first generation, leading to the diversified chemical structures. Thus, these fascinating reactions could be considered as a promising chemical model for studying the unique chemistry of possible penta-coordinated phosphorus intermediates in the process of RNA self-splicing, hydrolysis and fusion for gene transcription and biological information storage.
Penta-coordinated phosphoranes (ab2) with a five-member cycle and three ligands would simultaneously exchange with themselves under base catalysis to form three different penta-oxy phosphoranes with all the combinatorial ligands referred as a3, b3, and a2b. If we consider a3 and b3 as parents, the products obtained from exchange, namely a2b and ab2, could be regarded as the offspring of the first generation, leading to the diversified chemical structures. Thus, these fascinating reactions could be considered as a promising chemical model for studying the unique chemistry of possible penta-coordinated phosphorus intermediates in the process of RNA self-splicing, hydrolysis and fusion for gene transcription and biological information storage.
2019, 39(8): 2323-2327
doi: 10.6023/cjoc201903077
Abstract:
A mild and efficient nBu4NBr-mediated oxidative cycloaromatization to prepare β-carbolines from readily available tryptophans and N-methylaniline is described. The present metal free protocol is complementary to the existing methods for the synthesis of aromatic β-carbolines.
A mild and efficient nBu4NBr-mediated oxidative cycloaromatization to prepare β-carbolines from readily available tryptophans and N-methylaniline is described. The present metal free protocol is complementary to the existing methods for the synthesis of aromatic β-carbolines.
2019, 39(8): 2333-2337
doi: 10.6023/cjoc201903036
Abstract:
A simple, mild, and high yielding procedure for the iodination of alcohols using a combination of NaBH4 and I2 is described. The effectiveness of the protocol is achieved with benzylic alcohols and primary alkylic alcohols whereas allylic and secondary alcohols are found to be unreactive.
A simple, mild, and high yielding procedure for the iodination of alcohols using a combination of NaBH4 and I2 is described. The effectiveness of the protocol is achieved with benzylic alcohols and primary alkylic alcohols whereas allylic and secondary alcohols are found to be unreactive.
2019, 39(8): 2338-2342
doi: 10.6023/cjoc201902016
Abstract:
Direct synthesis of organophosphorus compounds from white phosphorus (P4) is of great significance because this process avoids the industry pollution synthetic methods and provides the possibilities for many novel phosphorus-containing compounds. A trinuclear rare-earth metal complex[{(η5-C5Me5)LuCl}3(THF)P6] [Li(THF)4] from lutetacyclopentadiene mediated P4 functionalization was isolated and characterized. This novel complex contains a bicyclo[3.1.0]-P64- ligand which is an unreported type. X-ray diffraction analysis shows that the bicyclo[3.1.0]-P64- ligand adopts a boat-like conformation. Three lutetium atoms coordinate to this ligand in η1, η3, η3 mode, respectively, and a novel[P6Lu3] cage has been formed. Density functional theory (DFT) calculations indicate that there are two three-center two-electron bonds.
Direct synthesis of organophosphorus compounds from white phosphorus (P4) is of great significance because this process avoids the industry pollution synthetic methods and provides the possibilities for many novel phosphorus-containing compounds. A trinuclear rare-earth metal complex[{(η5-C5Me5)LuCl}3(THF)P6] [Li(THF)4] from lutetacyclopentadiene mediated P4 functionalization was isolated and characterized. This novel complex contains a bicyclo[3.1.0]-P64- ligand which is an unreported type. X-ray diffraction analysis shows that the bicyclo[3.1.0]-P64- ligand adopts a boat-like conformation. Three lutetium atoms coordinate to this ligand in η1, η3, η3 mode, respectively, and a novel[P6Lu3] cage has been formed. Density functional theory (DFT) calculations indicate that there are two three-center two-electron bonds.
2019, 39(8): 2317-2322
doi: 10.6023/cjoc201905020
Abstract:
In order to discover more potent antifungal, a series of 2-aryl-3, 4-dihydroisoquinolin-2-iums were reasonable designed and productive synthesized by introducing benzoic acid and phenol pharmacophores into the 2-position of isoquinoline. Their structures were identified by NMR and HRMS. The preliminary in vitro antifungal results showed that most of the title compounds exhibited moderate to significant inhibitory activities against various phytopathogenic fungi at 50 mg·mL-1, and were equal to controls (chlorothalonil, carbendazim). The concentration of 50% inhibition rate (EC50) of 2-(3-ethoxycarbonyl-phenyl)-3, 4-dihydroisoquinolin-2-ium (4j) against R. solani was 3.8495 mg·mL-1, which was significantly superior to chlorothalonil (4.6328 mg·mL-1). All the EC50 values of 5 compounds (7.4583~15.4495 mg·mL-1) against R. cerealis were better than chlorothalonil (16.0137 mg·mL-1), and 2-(4-methoxycarbonylphenyl)-3, 4-dihydroisoquinolin-2-ium (4f) is the best one. The present results provide valuable information for development of plant-based antifungal agents.
In order to discover more potent antifungal, a series of 2-aryl-3, 4-dihydroisoquinolin-2-iums were reasonable designed and productive synthesized by introducing benzoic acid and phenol pharmacophores into the 2-position of isoquinoline. Their structures were identified by NMR and HRMS. The preliminary in vitro antifungal results showed that most of the title compounds exhibited moderate to significant inhibitory activities against various phytopathogenic fungi at 50 mg·mL-1, and were equal to controls (chlorothalonil, carbendazim). The concentration of 50% inhibition rate (EC50) of 2-(3-ethoxycarbonyl-phenyl)-3, 4-dihydroisoquinolin-2-ium (4j) against R. solani was 3.8495 mg·mL-1, which was significantly superior to chlorothalonil (4.6328 mg·mL-1). All the EC50 values of 5 compounds (7.4583~15.4495 mg·mL-1) against R. cerealis were better than chlorothalonil (16.0137 mg·mL-1), and 2-(4-methoxycarbonylphenyl)-3, 4-dihydroisoquinolin-2-ium (4f) is the best one. The present results provide valuable information for development of plant-based antifungal agents.
