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2020 Volume 40 Issue 10
2020, 40(10): 3017-3025
doi: 10.6023/cjoc202005083
Abstract:
Our recent research efforts on the synthesis of nonplanar nanographenes bearing tribenzotriquinacene or fenestrindane skeleton are summarized. Wizard hat-shaped or saddle-shaped nanographenes could be prepared using a non-classical Scholl-type cycloheptatriene formation or 19-membered ring macrocyclization. The key to the success of these transformation relies on the proper installation of the electron rich aryl functional groups in the bay areas of these molecular motifs. The three-dimensional structures of some of the nanographenes were determined by X-ray crystallography. Furthermore, these carbon-rich π-conjugated molecules are also showed to have interesting photophysical, self-assoication and host-guest complexation properties.
Our recent research efforts on the synthesis of nonplanar nanographenes bearing tribenzotriquinacene or fenestrindane skeleton are summarized. Wizard hat-shaped or saddle-shaped nanographenes could be prepared using a non-classical Scholl-type cycloheptatriene formation or 19-membered ring macrocyclization. The key to the success of these transformation relies on the proper installation of the electron rich aryl functional groups in the bay areas of these molecular motifs. The three-dimensional structures of some of the nanographenes were determined by X-ray crystallography. Furthermore, these carbon-rich π-conjugated molecules are also showed to have interesting photophysical, self-assoication and host-guest complexation properties.
2020, 40(10): 3026-3043
doi: 10.6023/cjoc202006042
Abstract:
The natural siderophore is a class of small-molecule iron ion chelating agents secreted by bacteria, which can be recognized by specific outer membrane receptors and transported into cytoplasm to provide iron for bacteria. Using this characteristic of siderophore, antibiotics can be coupled with them and enter into bacteria through the bacterial iron uptake system. This strategy is called "Trojan horse" strategy. Recently, cefiderocol, the first siderophore-antibiotic conjugate, was approved for marketing, which has aroused accumulated interest of scientists and pharmaceutical companies in this field. This paper provides a comprehensive review of the progress in antibiotics conjugated with siderophores from three aspects:the types of siderophore molecules, antibiotics with different action mechanisms, and the role of linkers. The basic relationship between anti-bacterial activity and three moieties of this novel type of anti-bacterial agents has been revealed. This review will provide a reference for the development of new antibiotics conjugated with siderophores.
The natural siderophore is a class of small-molecule iron ion chelating agents secreted by bacteria, which can be recognized by specific outer membrane receptors and transported into cytoplasm to provide iron for bacteria. Using this characteristic of siderophore, antibiotics can be coupled with them and enter into bacteria through the bacterial iron uptake system. This strategy is called "Trojan horse" strategy. Recently, cefiderocol, the first siderophore-antibiotic conjugate, was approved for marketing, which has aroused accumulated interest of scientists and pharmaceutical companies in this field. This paper provides a comprehensive review of the progress in antibiotics conjugated with siderophores from three aspects:the types of siderophore molecules, antibiotics with different action mechanisms, and the role of linkers. The basic relationship between anti-bacterial activity and three moieties of this novel type of anti-bacterial agents has been revealed. This review will provide a reference for the development of new antibiotics conjugated with siderophores.
2020, 40(10): 3044-3064
doi: 10.6023/cjoc202005095
Abstract:
Transition metal-catalyzed asymmetric oxidation, as one of important research targets of chiral synthesis, provides a direct, practical route for the synthesis of various chiral bioactive products and drugs, and has received much attention. The recent progress of the methods of transition metal-catalyzed asymmetric oxidation, especially, asymmetric oxidative functionalization of olefins, C-H bond asymmetric oxidation reaction, asymmetric BV oxidation and sulfide asymmetric oxidation is elaborated. Outlook of those issuesis is also discussed.
Transition metal-catalyzed asymmetric oxidation, as one of important research targets of chiral synthesis, provides a direct, practical route for the synthesis of various chiral bioactive products and drugs, and has received much attention. The recent progress of the methods of transition metal-catalyzed asymmetric oxidation, especially, asymmetric oxidative functionalization of olefins, C-H bond asymmetric oxidation reaction, asymmetric BV oxidation and sulfide asymmetric oxidation is elaborated. Outlook of those issuesis is also discussed.
2020, 40(10): 3065-3077
doi: 10.6023/cjoc202005020
Abstract:
As one of the most important click reactions, the copper-catalyzed azide-alkyne cycloaddition (CuAAC) has found widespread applications. Nevertheless, the exploitation of enantioselective CuAAC remains largely undeveloped. Although the reaction itself does not generate chiral elements, the enantioselective CuAAC can be realized via the desymmetrization of prochiral dialkynes or diazides, as well as the kinetic resolution of racemic azides or terminal alkynes. Notably, enantioselective CuAAC provides efficient access to structurally diverse enantioenriched compounds featuring an azide, terminal alkyne or 1, 4-disubstituted 1, 2, 3-triazoles, which are valuable structural units in organic synthesis or medicinal chemistry. Since the first highly enantioselective CuAAC reaction via desymmetrization of prochiral diynes was reported in 2013, substantial progress has been made in this research area. To date, enantioselective CuAAC has been successfully applied to the construction of central chirality, axial chirality and planar chirality. The recent exciting achievements are summarized, the challenges in this context are briefly discussed, and the synthetic opportunities for future development are outlined.
As one of the most important click reactions, the copper-catalyzed azide-alkyne cycloaddition (CuAAC) has found widespread applications. Nevertheless, the exploitation of enantioselective CuAAC remains largely undeveloped. Although the reaction itself does not generate chiral elements, the enantioselective CuAAC can be realized via the desymmetrization of prochiral dialkynes or diazides, as well as the kinetic resolution of racemic azides or terminal alkynes. Notably, enantioselective CuAAC provides efficient access to structurally diverse enantioenriched compounds featuring an azide, terminal alkyne or 1, 4-disubstituted 1, 2, 3-triazoles, which are valuable structural units in organic synthesis or medicinal chemistry. Since the first highly enantioselective CuAAC reaction via desymmetrization of prochiral diynes was reported in 2013, substantial progress has been made in this research area. To date, enantioselective CuAAC has been successfully applied to the construction of central chirality, axial chirality and planar chirality. The recent exciting achievements are summarized, the challenges in this context are briefly discussed, and the synthetic opportunities for future development are outlined.
2020, 40(10): 3078-3093
doi: 10.6023/cjoc202005072
Abstract:
C(sp3)-C(sp3) bond coupling is of great significance in organic synthesis, among which reductive homocoupling has showed its special superiority in construction of symmetrical molecular structures. These reactions are usually operationally simple, which utilize organohalides as substrates, avoiding the handling of highly reactive organometallic reagents. The use of non-precise metals as the catalyst makes reductive homocouplings amenable for large-scale synthesis. Improved efficiency and selectivity have been observed in systems involving photoredox catalytic processes, ionic-liquids, and inorganic nanomaterials. This review aims to summarize the development of reductive couplings. In this review, various reductive homocouplings are summarized, where transition metals, such as cobalt, nickel, copper, titanium, and rhodium are involved. Photo-mediated reductive couplings are then highlighted followed by a discussion on applications of reductive couplings in natural products synthesis and polymer sciences.
C(sp3)-C(sp3) bond coupling is of great significance in organic synthesis, among which reductive homocoupling has showed its special superiority in construction of symmetrical molecular structures. These reactions are usually operationally simple, which utilize organohalides as substrates, avoiding the handling of highly reactive organometallic reagents. The use of non-precise metals as the catalyst makes reductive homocouplings amenable for large-scale synthesis. Improved efficiency and selectivity have been observed in systems involving photoredox catalytic processes, ionic-liquids, and inorganic nanomaterials. This review aims to summarize the development of reductive couplings. In this review, various reductive homocouplings are summarized, where transition metals, such as cobalt, nickel, copper, titanium, and rhodium are involved. Photo-mediated reductive couplings are then highlighted followed by a discussion on applications of reductive couplings in natural products synthesis and polymer sciences.
2020, 40(10): 3094-3111
doi: 10.6023/cjoc202006005
Abstract:
C-Glycosides are a class of carbohydrates with a variety of biological activities, and the construction of their unique C-C glycosidic bond is a hot and challenging topic in carbohydrate chemistry. The formation of new C-C bond from carbon-carbon double bond is a common strategy in organic chemistry. With the rapid development of ene-chemistry, great progress in the synthesis of C-glycosides from glycal donors containing 1, 2-double bond has been made. In this review, the methods for the synthesis of C-glycosides based on glycals are summarized, including Ferrier Ⅰ-type C-glycosylation, Heck-type C-glycosylation, C-glycosylation of 1-substituted glycals using transition metal-catalyzed coupling reaction, Michael-type C-glycosylation of 2-substituted glycals, and radical addition type C-glycosylation of glycals.
C-Glycosides are a class of carbohydrates with a variety of biological activities, and the construction of their unique C-C glycosidic bond is a hot and challenging topic in carbohydrate chemistry. The formation of new C-C bond from carbon-carbon double bond is a common strategy in organic chemistry. With the rapid development of ene-chemistry, great progress in the synthesis of C-glycosides from glycal donors containing 1, 2-double bond has been made. In this review, the methods for the synthesis of C-glycosides based on glycals are summarized, including Ferrier Ⅰ-type C-glycosylation, Heck-type C-glycosylation, C-glycosylation of 1-substituted glycals using transition metal-catalyzed coupling reaction, Michael-type C-glycosylation of 2-substituted glycals, and radical addition type C-glycosylation of glycals.
2020, 40(10): 3120-3131
doi: 10.6023/cjoc202005071
Abstract:
Thiopeptide antibiotics are a class of natural products with polythiophene (oxazol) polypeptides, which are rich in sulfur and highly modified. They are produced by secondary metabolism of microorganisms and have good biological activities. Developing thiopeptides into clinic is currently a challenge partly due to their low aqueous solubility and associated poor bioavailability. On the basis of understanding the mechanism of their biosynthesis, the method of obtaining thiopeptide analogues via reasonable bioengineering has become the research focus of biologists. In this paper, the advances in structural modifications of bicyclic thiopeptides by taking thiostrepton and nosiheptide as representatives are reviewed.
Thiopeptide antibiotics are a class of natural products with polythiophene (oxazol) polypeptides, which are rich in sulfur and highly modified. They are produced by secondary metabolism of microorganisms and have good biological activities. Developing thiopeptides into clinic is currently a challenge partly due to their low aqueous solubility and associated poor bioavailability. On the basis of understanding the mechanism of their biosynthesis, the method of obtaining thiopeptide analogues via reasonable bioengineering has become the research focus of biologists. In this paper, the advances in structural modifications of bicyclic thiopeptides by taking thiostrepton and nosiheptide as representatives are reviewed.
2020, 40(10): 3132-3153
doi: 10.6023/cjoc202005092
Abstract:
Versatile heterocyclic skeletons extensively exist in structures of natural products, drug molecules and organic materials, and have been synthesized through various strategies reported in literatures. Among them, the 1, 3-dipolar cycloaddition is the most impressive class to build the related heterocycles. In the past, organic chemists generally employed[3+2] cycloaddition of 1, 3-dipoles to assemble five-membered rings. As modern chemistry developes, researchers further turn their attention to the[3+3], [3+4], [3+5] and[3+6] cycloadditions, to construct six-, seven-, eight- and bridge-heterocyclic compounds. At present, review articles with topics on 1, 3-dipolar cycloaddition mainly focus on[3+2] cycloaddition. Herein, A topic on[3+n] (n ≥ 3) cycloaddition of 1, 3-dipoles, with comments on the developed methodologies is present and the outlook in this field is proposed.
Versatile heterocyclic skeletons extensively exist in structures of natural products, drug molecules and organic materials, and have been synthesized through various strategies reported in literatures. Among them, the 1, 3-dipolar cycloaddition is the most impressive class to build the related heterocycles. In the past, organic chemists generally employed[3+2] cycloaddition of 1, 3-dipoles to assemble five-membered rings. As modern chemistry developes, researchers further turn their attention to the[3+3], [3+4], [3+5] and[3+6] cycloadditions, to construct six-, seven-, eight- and bridge-heterocyclic compounds. At present, review articles with topics on 1, 3-dipolar cycloaddition mainly focus on[3+2] cycloaddition. Herein, A topic on[3+n] (n ≥ 3) cycloaddition of 1, 3-dipoles, with comments on the developed methodologies is present and the outlook in this field is proposed.
2020, 40(10): 3154-3165
doi: 10.6023/cjoc202005043
Abstract:
As organocatalysts, organic base catalysts play an important role in the quest for optically pure compounds. Chiral iminophosphoranes, being organosuperbases, are very stable under air and moisture conditions, thereby providing an attractive platform for the design of various asymmetric organocatalysts. The recent achievements concerning chiral iminophosphoranes in the development of both organocatalysis and their applications in asymmetric synthesis are summarized and discussed.
As organocatalysts, organic base catalysts play an important role in the quest for optically pure compounds. Chiral iminophosphoranes, being organosuperbases, are very stable under air and moisture conditions, thereby providing an attractive platform for the design of various asymmetric organocatalysts. The recent achievements concerning chiral iminophosphoranes in the development of both organocatalysis and their applications in asymmetric synthesis are summarized and discussed.
2020, 40(10): 3166-3176
doi: 10.6023/cjoc202005028
Abstract:
The anislactone type sesquiterpenoids, (-)-merrilactones A-C and anislactones A-B, contain[5-5] bicyclic carbocyclic skeleton, two γ-butyrolactone structural units, featuring congested stereocenters and a high oxidation level. This type of natural products shows potent neurotrophic activity. Particularly, (-)-merrilactone A exhibits excellent neurotrophic activity even at lower concentration with potential for treating neurodisease such as Elzheimer disease. Due to their complex caged structures and excellent biologic profiles, the synthesis of aislactone-type sesquiterpenoids has attracted considerable attention from synthetic communities. This article summarizes the recent advances in the synthesis of this type of sesquiterpenoids.
The anislactone type sesquiterpenoids, (-)-merrilactones A-C and anislactones A-B, contain[5-5] bicyclic carbocyclic skeleton, two γ-butyrolactone structural units, featuring congested stereocenters and a high oxidation level. This type of natural products shows potent neurotrophic activity. Particularly, (-)-merrilactone A exhibits excellent neurotrophic activity even at lower concentration with potential for treating neurodisease such as Elzheimer disease. Due to their complex caged structures and excellent biologic profiles, the synthesis of aislactone-type sesquiterpenoids has attracted considerable attention from synthetic communities. This article summarizes the recent advances in the synthesis of this type of sesquiterpenoids.
2020, 40(10): 3177-3195
doi: 10.6023/cjoc202005016
Abstract:
In the past two decades, the development and application of bench-stable electrophilic difluoromethylating reagents have attracted considerable attention. Consequently, some progress in this area has been ongoing recently. Electrophilic difluoromethylating reagents play a very important role in the synthesis of fluorine-containing compounds, due to their capability of readily transferring difluoromethyl moiety (CF2H) into wide range of nucleophiles, as well as being used as difluoromethyl radical(•CF2H) precursorfor radical difluoromethylations. However, the electrophilic difluoromethylating reagents and application therein remain still underdeveloped in comparison with nucleophilic ones. The research advance in electrophilic difluoromethylating reagents in past two decades is reviewed.
In the past two decades, the development and application of bench-stable electrophilic difluoromethylating reagents have attracted considerable attention. Consequently, some progress in this area has been ongoing recently. Electrophilic difluoromethylating reagents play a very important role in the synthesis of fluorine-containing compounds, due to their capability of readily transferring difluoromethyl moiety (CF2H) into wide range of nucleophiles, as well as being used as difluoromethyl radical(•CF2H) precursorfor radical difluoromethylations. However, the electrophilic difluoromethylating reagents and application therein remain still underdeveloped in comparison with nucleophilic ones. The research advance in electrophilic difluoromethylating reagents in past two decades is reviewed.
2020, 40(10): 3196-3202
doi: 10.6023/cjoc202005056
Abstract:
Medium rings (7~9 membered) widely exist in a variety of natural products that often have important bio-activities, thereby the development of economical and highly efficient synthetic routes to them has received intensive attention. Recent advances on transition metal-catalyzed π-unsaturated compounds inserting into C-H bonds for the construction of medium rings are summarized. According to different strategies that were used to stabilize organometallic intermediates, these methods can be divided into four types, and each of which was described from various aspects including its progress, characteristics, reaction types and mechanisms.
Medium rings (7~9 membered) widely exist in a variety of natural products that often have important bio-activities, thereby the development of economical and highly efficient synthetic routes to them has received intensive attention. Recent advances on transition metal-catalyzed π-unsaturated compounds inserting into C-H bonds for the construction of medium rings are summarized. According to different strategies that were used to stabilize organometallic intermediates, these methods can be divided into four types, and each of which was described from various aspects including its progress, characteristics, reaction types and mechanisms.
2020, 40(10): 3203-3213
doi: 10.6023/cjoc202005079
Abstract:
Carboranes are a class of carbon-boron molecular clusters with exceptional thermal and chemical stabilities. They are finding a variety of applications in medicine, materials, and coordination/organometallic chemistry as functional building blocks. To this end, the selective functionalization of carboranes has received growing research interests. Transition metal-promoted multicomponent cascade reactions are particularly attractive since they have the advantages of step- and atom- economy for the construction of complex products from readily available starting materials by simple operations. The recent advances in transition metal-promoted multicomponent cascade reactions for selective functionalization of carboranes are summarized in this focus review. The related reaction mechanisms and challenges in this research area are also discussed.
Carboranes are a class of carbon-boron molecular clusters with exceptional thermal and chemical stabilities. They are finding a variety of applications in medicine, materials, and coordination/organometallic chemistry as functional building blocks. To this end, the selective functionalization of carboranes has received growing research interests. Transition metal-promoted multicomponent cascade reactions are particularly attractive since they have the advantages of step- and atom- economy for the construction of complex products from readily available starting materials by simple operations. The recent advances in transition metal-promoted multicomponent cascade reactions for selective functionalization of carboranes are summarized in this focus review. The related reaction mechanisms and challenges in this research area are also discussed.
2020, 40(10): 3214-3236
doi: 10.6023/cjoc202005065
Abstract:
Chiral spirooxindoles have captured huge attention from researchers in the area of organic chemistry and medicinal chemistry owing to their prevalence in various alkaloid natural products and pharmacologically active agents. In recent year, chiral bifunctional squaramide-catalyzed asymmetric cascade reaction of oxindoles or oxindole derivatives has become an efficient synthetic method for the construction of chiral spirooxindoes. In this review, the remarkable progress and advances in bifunctional squaramide-catalyzed asymmetric cascade reactions for the synthesis of spirooxindole derivatives from 2015 are summarized and discussed based on the different types of catalytic reactions.
Chiral spirooxindoles have captured huge attention from researchers in the area of organic chemistry and medicinal chemistry owing to their prevalence in various alkaloid natural products and pharmacologically active agents. In recent year, chiral bifunctional squaramide-catalyzed asymmetric cascade reaction of oxindoles or oxindole derivatives has become an efficient synthetic method for the construction of chiral spirooxindoes. In this review, the remarkable progress and advances in bifunctional squaramide-catalyzed asymmetric cascade reactions for the synthesis of spirooxindole derivatives from 2015 are summarized and discussed based on the different types of catalytic reactions.
2020, 40(10): 3237-3248
doi: 10.6023/cjoc202005030
Abstract:
As an antivirus drug, remdesivir is currently in clinical studies for the treatment of COVID-19. Remdesivir is a prodrug originally developed by Gilead for the treatment of Ebola. The prodrug nucleotide (ProTide) technology is a prodrug-designing strategy developed by McGuigan and co-workers, in which a phosphoramidate side-chain is covalently attached to the hydroxy group of a drug molecule in order to enhance the cell permeability and metabolic activation efficiency. This approach has proved to be very successful in the identification of nucleoside analogues with antiviral or antitumor activities. It is also adapted in the application of non-nucleoside agents, such as neurodegeneration therapeutics, further demonstrating its usefulness in drug discovery. The chirality of the pentavalent phosphorous plays a significant role in the bioactivity of a ProTide molecule. Therefore, the efficient synthesis of such chemical scaffold in a highly enantioselective manner is very desirable and has intrigued great interests from both academia and pharmaceutical industry. In this review, based on the reactions employing optically pure P(V) precursors or P-racemic P(V) precursors, the recent advances on the stereoselective assembly of ProTide compounds are summarized. Various innovative strategies, including (dynamic) kinetic resolutions, were implemented to construct the vital P-stereogenic center with high regio- and stereo-selectivity. It is notable that several methods could be performed at kilogram scale, which are highlighted to showcase their practical values in the process chemistry. The asymmetric synthesis of enantiopure phosphoramidate precursors is illustrated in detail which will be informative for future drug development. Moreover, the clinical performance of some investigational ProTide drugs is also briefly discussed.
As an antivirus drug, remdesivir is currently in clinical studies for the treatment of COVID-19. Remdesivir is a prodrug originally developed by Gilead for the treatment of Ebola. The prodrug nucleotide (ProTide) technology is a prodrug-designing strategy developed by McGuigan and co-workers, in which a phosphoramidate side-chain is covalently attached to the hydroxy group of a drug molecule in order to enhance the cell permeability and metabolic activation efficiency. This approach has proved to be very successful in the identification of nucleoside analogues with antiviral or antitumor activities. It is also adapted in the application of non-nucleoside agents, such as neurodegeneration therapeutics, further demonstrating its usefulness in drug discovery. The chirality of the pentavalent phosphorous plays a significant role in the bioactivity of a ProTide molecule. Therefore, the efficient synthesis of such chemical scaffold in a highly enantioselective manner is very desirable and has intrigued great interests from both academia and pharmaceutical industry. In this review, based on the reactions employing optically pure P(V) precursors or P-racemic P(V) precursors, the recent advances on the stereoselective assembly of ProTide compounds are summarized. Various innovative strategies, including (dynamic) kinetic resolutions, were implemented to construct the vital P-stereogenic center with high regio- and stereo-selectivity. It is notable that several methods could be performed at kilogram scale, which are highlighted to showcase their practical values in the process chemistry. The asymmetric synthesis of enantiopure phosphoramidate precursors is illustrated in detail which will be informative for future drug development. Moreover, the clinical performance of some investigational ProTide drugs is also briefly discussed.
2020, 40(10): 3249-3261
doi: 10.6023/cjoc202006019
Abstract:
Single-walled carbon nanotubes (SWNTs) prepared by present methods are a mixture of semiconducting and metallic ones, which need to be separated and purified to give them full play with their excellent properties and for their attractive applications. Among numerous developed methods, the selective separation of semiconducting and metallic SWNTs by polymer non-covalent interactions is considered to be the most simple, efficient and no-damage to carbon nanotube structure and properties method. So far, a lot of works have been reported, and many polymer systems have been developed. Meanwhile, various separation and purification mechanisms have been proposed, but there are still no unified and convincing understandings. In this review, the reported SWNT solubilization and selective separation works are summarized, the interactions between polymer and SWNTs are analyzed, and the effects of polymer structures, molecular weights, side chain lengths, polymer/SMNT ratio, temperature, and solvent are focally discussed. After comparing various separating mechanisms, our own understandings and views are put forward.
Single-walled carbon nanotubes (SWNTs) prepared by present methods are a mixture of semiconducting and metallic ones, which need to be separated and purified to give them full play with their excellent properties and for their attractive applications. Among numerous developed methods, the selective separation of semiconducting and metallic SWNTs by polymer non-covalent interactions is considered to be the most simple, efficient and no-damage to carbon nanotube structure and properties method. So far, a lot of works have been reported, and many polymer systems have been developed. Meanwhile, various separation and purification mechanisms have been proposed, but there are still no unified and convincing understandings. In this review, the reported SWNT solubilization and selective separation works are summarized, the interactions between polymer and SWNTs are analyzed, and the effects of polymer structures, molecular weights, side chain lengths, polymer/SMNT ratio, temperature, and solvent are focally discussed. After comparing various separating mechanisms, our own understandings and views are put forward.
2020, 40(10): 3262-3278
doi: 10.6023/cjoc202005008
Abstract:
Iridium-catalyzed asymmetric allylic substitution reaction has become one of the most important methods for the synthesis of chiral compounds due to its exceptional branched regioselectivity and excellent enantioselectivity. The scope of nucleophiles will be further expanded by synergetic catalysis system of iridium and other catalysts (organocatalysts, other transition metal catalysts). Besides, it is possible to improve the enantioselectivity of the reaction and even realize the stereodivergent synthesis of the products with multiple stereocenters. The progress in the field of catalytic asymmetric allylic substitutions through synergetic iridium and organocatalysis or other transition metal catalysis is summarized. These reactions are classified according to the types of catalysts (aminocatalyst, phase transfer catalyst, Brønsted acid, Lewis base, transition metal). Meanwhile, the mechanism of representative reactions, the existing problems and the prospects in this area are briefly described.
Iridium-catalyzed asymmetric allylic substitution reaction has become one of the most important methods for the synthesis of chiral compounds due to its exceptional branched regioselectivity and excellent enantioselectivity. The scope of nucleophiles will be further expanded by synergetic catalysis system of iridium and other catalysts (organocatalysts, other transition metal catalysts). Besides, it is possible to improve the enantioselectivity of the reaction and even realize the stereodivergent synthesis of the products with multiple stereocenters. The progress in the field of catalytic asymmetric allylic substitutions through synergetic iridium and organocatalysis or other transition metal catalysis is summarized. These reactions are classified according to the types of catalysts (aminocatalyst, phase transfer catalyst, Brønsted acid, Lewis base, transition metal). Meanwhile, the mechanism of representative reactions, the existing problems and the prospects in this area are briefly described.
2020, 40(10): 3279-3288
doi: 10.6023/cjoc202004022
Abstract:
Graphene and graphene oxide possess unique structure and excellent properties, and have become popular potential materials in biology, information, energy and other fields in recent years. The high-quality nanocomposites were obtained by hybridizing graphene-based materials with functional molecules, polymers and nanoparticles. Besides the modification via weak interaction, covalent modification of graphene and graphene oxide via organic reaction can stably and effectively optimize the structure, enhance their performances and extend their applications. In this review, the diverse approaches of chemically covalent modification of graphene and graphene oxide are reviewed via esterification, acylation, Williamson reaction, Eschenmoser-Claisen[3 , 3 ] σ rearrangement and click chemistry, and the future development trend is prospected.
Graphene and graphene oxide possess unique structure and excellent properties, and have become popular potential materials in biology, information, energy and other fields in recent years. The high-quality nanocomposites were obtained by hybridizing graphene-based materials with functional molecules, polymers and nanoparticles. Besides the modification via weak interaction, covalent modification of graphene and graphene oxide via organic reaction can stably and effectively optimize the structure, enhance their performances and extend their applications. In this review, the diverse approaches of chemically covalent modification of graphene and graphene oxide are reviewed via esterification, acylation, Williamson reaction, Eschenmoser-Claisen[
2020, 40(10): 3289-3299
doi: 10.6023/cjoc202003014
Abstract:
Gracilioethers and hippolachnin A were isolated from marine sponge. Gracilioethers showed antimalarial activity while hippolachnin A exhibited strong antifungal activity. Their fascinating structures and outstanding biological activities have attracted attentions from chemists. Progress on the synthesis of gracilioethers with tricyclic skeleton and hippolachnin A are reviewed in terms of the key strategies employed.
Gracilioethers and hippolachnin A were isolated from marine sponge. Gracilioethers showed antimalarial activity while hippolachnin A exhibited strong antifungal activity. Their fascinating structures and outstanding biological activities have attracted attentions from chemists. Progress on the synthesis of gracilioethers with tricyclic skeleton and hippolachnin A are reviewed in terms of the key strategies employed.
2020, 40(10): 3112-3119
doi: 10.6023/cjoc202005094
Abstract:
The protection/deprotection of functional group is one of the fundamental technologies in organic synthesis. An ideal protecting group needs to satisfy the following issues:facile introduction, stability and facile deprotection. Protection of an acetylenic hydrogen is often necessary because of its acidity. In this review, the recent progress of protecting groups for terminal alkyne is highlighted. Based on different polarity of protecting groups, less polar protecting groups such as trimethylsilyl (TMS), trimethylgermanium group (Me3Ge) and high polar protecting groups like (3-cyanopropyl)dimethylsilyl (CPDMS), (3-cyanopropyl)diisopropylsilyl (CPDIPS) and diphenylphosphoryl (Ph2P(O)) are introduced in detail.
The protection/deprotection of functional group is one of the fundamental technologies in organic synthesis. An ideal protecting group needs to satisfy the following issues:facile introduction, stability and facile deprotection. Protection of an acetylenic hydrogen is often necessary because of its acidity. In this review, the recent progress of protecting groups for terminal alkyne is highlighted. Based on different polarity of protecting groups, less polar protecting groups such as trimethylsilyl (TMS), trimethylgermanium group (Me3Ge) and high polar protecting groups like (3-cyanopropyl)dimethylsilyl (CPDMS), (3-cyanopropyl)diisopropylsilyl (CPDIPS) and diphenylphosphoryl (Ph2P(O)) are introduced in detail.
2020, 40(10): 3300-3306
doi: 10.6023/cjoc202005011
Abstract:
A facile and efficient method for the synthesis of novel 3-((trifluoromethyl)thio)-2-aminoindoles through copper (I)-promoted trifluoromethylthiolation of 3-diazoindolin-2-imines with AgSCF3 is reported. This methodology features a broad substrate scope of diazo compounds, economical copper(I) catalyst, readily available and stable diazo materials and trifluoromethylthiolating reagent, mild reaction conditions, short reaction time and water assisted higher yields.
A facile and efficient method for the synthesis of novel 3-((trifluoromethyl)thio)-2-aminoindoles through copper (I)-promoted trifluoromethylthiolation of 3-diazoindolin-2-imines with AgSCF3 is reported. This methodology features a broad substrate scope of diazo compounds, economical copper(I) catalyst, readily available and stable diazo materials and trifluoromethylthiolating reagent, mild reaction conditions, short reaction time and water assisted higher yields.
2020, 40(10): 3314-3326
doi: 10.6023/cjoc202005048
Abstract:
A photocatalytic Z to E isomerization of monofluorostilbenes in the presence of visible light (blue LEDs) has been developed. The transformation, which proceeds through a selective energy transfer pathway with Ir(Ⅲ) complex, offers facile access to thermodynamically less stable E-monofluoroalkenes with synthetically useful efficiency (up to 96% yield, up to 91:9 E:Z). Mild reaction conditions, good functional groups tolerance, and broad substrate scope were observed. Furthermore, the synthetic utility of this method is demonstrated by the rapid synthesis of monofluorinated cis-DMU-212 analogue E-30.
A photocatalytic Z to E isomerization of monofluorostilbenes in the presence of visible light (blue LEDs) has been developed. The transformation, which proceeds through a selective energy transfer pathway with Ir(Ⅲ) complex, offers facile access to thermodynamically less stable E-monofluoroalkenes with synthetically useful efficiency (up to 96% yield, up to 91:9 E:Z). Mild reaction conditions, good functional groups tolerance, and broad substrate scope were observed. Furthermore, the synthetic utility of this method is demonstrated by the rapid synthesis of monofluorinated cis-DMU-212 analogue E-30.
2020, 40(10): 3338-3346
doi: 10.6023/cjoc202005069
Abstract:
A series of P, O-type indolylphosphine ligands with different substituted variants have been synthesized by a simple one-pot protocol from readily available and inexpensive materials. These ligands show "substituent effect" with respected to the efficacy in promoting palladium-catalyzed Suzuki-Miyaura cross-coupling of aryl chlorides. This new Pd/L1 catalyst system particularly allows the catalyst loading reaching the level of 0.01 mol% Pd.
A series of P, O-type indolylphosphine ligands with different substituted variants have been synthesized by a simple one-pot protocol from readily available and inexpensive materials. These ligands show "substituent effect" with respected to the efficacy in promoting palladium-catalyzed Suzuki-Miyaura cross-coupling of aryl chlorides. This new Pd/L1 catalyst system particularly allows the catalyst loading reaching the level of 0.01 mol% Pd.
2020, 40(10): 3347-3353
doi: 10.6023/cjoc202005033
Abstract:
A synthetic strategy based on a ring expansion reaction to introduce eight-membered rings into polycyclic aromatic frameworks is reported. The octagon-embedded hexabenzocoronene synthesized with this strategy features a saddle-shaped polycyclic framework as revealed by the single crystal X-ray crystallography.
A synthetic strategy based on a ring expansion reaction to introduce eight-membered rings into polycyclic aromatic frameworks is reported. The octagon-embedded hexabenzocoronene synthesized with this strategy features a saddle-shaped polycyclic framework as revealed by the single crystal X-ray crystallography.
2020, 40(10): 3362-3370
doi: 10.6023/cjoc202005090
Abstract:
tridentate P, N, N-donor pincer ligands bearing two or three stereocenters, 1-(4, 5-dihydro-oxazol-2-yl)-N-(2-(diphenylphosphanyl)benzyl)methanamines (oxpma), were synthesized starting from readily available amino acids in five or six steps. They were applied in palladium-catalyzed asymmetric allylic alkylation of allylic acetates to afford the desired products with high enantioselectivities (up to 96% ee).
tridentate P, N, N-donor pincer ligands bearing two or three stereocenters, 1-(4, 5-dihydro-oxazol-2-yl)-N-(2-(diphenylphosphanyl)benzyl)methanamines (oxpma), were synthesized starting from readily available amino acids in five or six steps. They were applied in palladium-catalyzed asymmetric allylic alkylation of allylic acetates to afford the desired products with high enantioselectivities (up to 96% ee).
2020, 40(10): 3371-3379
doi: 10.6023/cjoc202005064
Abstract:
Cu(Ⅱ)-mediated β-C-H alkynylation of acrylamides with terminal alkynes is described by employing amide-oxazoline bidentate auxiliary, forming the conjugated 1, 3-enynes. This protocol is characterized by its mild conditions, broad substarate scope and excellent regio- and stereo-selectivity.
Cu(Ⅱ)-mediated β-C-H alkynylation of acrylamides with terminal alkynes is described by employing amide-oxazoline bidentate auxiliary, forming the conjugated 1, 3-enynes. This protocol is characterized by its mild conditions, broad substarate scope and excellent regio- and stereo-selectivity.
2020, 40(10): 3380-3389
doi: 10.6023/cjoc202005089
Abstract:
Treatment of ButPCl2 with 2 equiv. of (2, 4, 6-Me3C6H2)(2-LiC6H4)NLi and (2, 6-Cl2C6H3)(2-LiC6H4)NLi, which were generated in situ by the interaction of (2, 4, 6-Me3C6H2)(2-BrC6H4)NH and (2, 6-Cl2C6H3)(2-BrC6H4)NH with 2 equiv. of BunLi, followed by quenching with water, afforded new tridentate diamine-phosphine compounds (o-(N-(2, 4, 6-Me3C6H2)-NH)C6H4)2PBut and (o-(N-(2, 6-Cl2C6H3)NH)C6H4)2PBut (denoted as H2(MesN2PBu-t) and H2(dcpN2PBu-t)), respectively. H2(MesN2PBu-t) and H2(dcpN2PBu-t) underwent amine-elimination reaction with[Fe(N(SiMe3)2)2]2 (0.5 equiv.) to afford iron(Ⅱ) complexes[(κ3-N, N, P-MesN2PBu-t)Fe(OEt2)] (1) and[(κ3-N, N, P-dcpN2PBu-t)Fe(OEt2)] (2) bearing tridentate diamido-phosphine ligands. Treatment of 1 with organic diazo compounds (p-tolyl)2CN2 and PhC(N2)CO2Et rendered the formation of diazo coordinated iron complexes[(κ3-N, N, P-MesN2PBu-t)Fe(η2-N, N-(p-tolyl)2CN2)] (3) and[(κ3-N, N, P-MesN2PBu-t)Fe(κ2-N, O-PhC(N2)-CO2Et)] (4), respectively. Complex 2 can catalyze the conversion of (p-tolyl)2CN2 to (p-tolyl)2C=NN=C(tolyl-p)2. Treatment of 2 with organic diazo compound DmpC(N2)H rendered the formation of a high-spin iron(Ⅱ) complex featuring the tridentate bisamido-phosphine ylide ligand[(κ3-N, N, C-dcpN2PBu-tCH, Dmp)Fe] (5). These complexes have been characterized by elemental analysis, 1H NMR, solution magnetic susceptibility measurements, zero-field 57Fe Mössbauer spectroscopy and single-crystal X-ray diffraction studies. The spectroscopic data in combination with theoretical study suggest that complex 3 can be viewed as a low-spin iron(IV) imido complex featuring an dianionic ligand[η2-N, N-(p-tolyl)2CN2]2-, whereas 4 has an intermediate-spin iron(Ⅲ) center that is antiferromagnetically coupled to a diazoalkane radical anion[κ2-N, O-PhC(N2)-CO2Et)]•1-.
Treatment of ButPCl2 with 2 equiv. of (2, 4, 6-Me3C6H2)(2-LiC6H4)NLi and (2, 6-Cl2C6H3)(2-LiC6H4)NLi, which were generated in situ by the interaction of (2, 4, 6-Me3C6H2)(2-BrC6H4)NH and (2, 6-Cl2C6H3)(2-BrC6H4)NH with 2 equiv. of BunLi, followed by quenching with water, afforded new tridentate diamine-phosphine compounds (o-(N-(2, 4, 6-Me3C6H2)-NH)C6H4)2PBut and (o-(N-(2, 6-Cl2C6H3)NH)C6H4)2PBut (denoted as H2(MesN2PBu-t) and H2(dcpN2PBu-t)), respectively. H2(MesN2PBu-t) and H2(dcpN2PBu-t) underwent amine-elimination reaction with[Fe(N(SiMe3)2)2]2 (0.5 equiv.) to afford iron(Ⅱ) complexes[(κ3-N, N, P-MesN2PBu-t)Fe(OEt2)] (1) and[(κ3-N, N, P-dcpN2PBu-t)Fe(OEt2)] (2) bearing tridentate diamido-phosphine ligands. Treatment of 1 with organic diazo compounds (p-tolyl)2CN2 and PhC(N2)CO2Et rendered the formation of diazo coordinated iron complexes[(κ3-N, N, P-MesN2PBu-t)Fe(η2-N, N-(p-tolyl)2CN2)] (3) and[(κ3-N, N, P-MesN2PBu-t)Fe(κ2-N, O-PhC(N2)-CO2Et)] (4), respectively. Complex 2 can catalyze the conversion of (p-tolyl)2CN2 to (p-tolyl)2C=NN=C(tolyl-p)2. Treatment of 2 with organic diazo compound DmpC(N2)H rendered the formation of a high-spin iron(Ⅱ) complex featuring the tridentate bisamido-phosphine ylide ligand[(κ3-N, N, C-dcpN2PBu-tCH, Dmp)Fe] (5). These complexes have been characterized by elemental analysis, 1H NMR, solution magnetic susceptibility measurements, zero-field 57Fe Mössbauer spectroscopy and single-crystal X-ray diffraction studies. The spectroscopic data in combination with theoretical study suggest that complex 3 can be viewed as a low-spin iron(IV) imido complex featuring an dianionic ligand[η2-N, N-(p-tolyl)2CN2]2-, whereas 4 has an intermediate-spin iron(Ⅲ) center that is antiferromagnetically coupled to a diazoalkane radical anion[κ2-N, O-PhC(N2)-CO2Et)]•1-.
2020, 40(10): 3390-3398
doi: 10.6023/cjoc202004044
Abstract:
A silver-catalyzed stereoselective addition reaction of functionalized alkynes with organic hypervalent iodine(Ⅲ) reagents as nucleophiles is reported, providing an approach to vinyl esters in high yields with excellent group tolerance. Intramolecular experiment demonstrates that the presence of aryl group considerably affects the cleavage of I-O bond within hypervalent iodine(Ⅲ) reagents, which is also responsible for the high stereoeselectivity observed in this catalytic system.
A silver-catalyzed stereoselective addition reaction of functionalized alkynes with organic hypervalent iodine(Ⅲ) reagents as nucleophiles is reported, providing an approach to vinyl esters in high yields with excellent group tolerance. Intramolecular experiment demonstrates that the presence of aryl group considerably affects the cleavage of I-O bond within hypervalent iodine(Ⅲ) reagents, which is also responsible for the high stereoeselectivity observed in this catalytic system.
Nickel-Catalyzed Regioselective Coupling Reaction of 3, 3, 3-Trifluoropropene with Arylzinc Reagents
2020, 40(10): 3307-3313
doi: 10.6023/cjoc202005082
Abstract:
3, 3, 3-Trifluoropropene (TFP) is an inexpensive and bulk industrial material and has important applications in the production of fluorinated polymers, refrigerant and so on. The use of TFP as a fluorine source enables access to a variety of fluorinated compounds. To date, important progress has been made in the transformations of TFP, however, most of the developed methods focused on the functionalization of carbon-carbon double bond of TFP. The controllable formation of fluorinated products via regio-selective functionalization of TFP received less attention. Herein, a nickel-catalyzed regioselective coupling of TFP with arylzinc reagents is described. By fine-tuning the reaction solvent, two different types of fluorinated products, gem-difluoroalkenes and Heck-type aryl-substituted TFPs, were obtained. The use of dioxane as the solvent led to a series of gem-difluoroalkenes in moderate to good yields with high regio-selectivity and functional group tolerance under mild reaction conditions. While, switching solvent from dioxane to N, N-dimethylformamide (DMF), the Heck-type aryl-substituted TFPs were obtained. This regioselective coupling provides an efficient route for applications of TFP in organic synthesis.
3, 3, 3-Trifluoropropene (TFP) is an inexpensive and bulk industrial material and has important applications in the production of fluorinated polymers, refrigerant and so on. The use of TFP as a fluorine source enables access to a variety of fluorinated compounds. To date, important progress has been made in the transformations of TFP, however, most of the developed methods focused on the functionalization of carbon-carbon double bond of TFP. The controllable formation of fluorinated products via regio-selective functionalization of TFP received less attention. Herein, a nickel-catalyzed regioselective coupling of TFP with arylzinc reagents is described. By fine-tuning the reaction solvent, two different types of fluorinated products, gem-difluoroalkenes and Heck-type aryl-substituted TFPs, were obtained. The use of dioxane as the solvent led to a series of gem-difluoroalkenes in moderate to good yields with high regio-selectivity and functional group tolerance under mild reaction conditions. While, switching solvent from dioxane to N, N-dimethylformamide (DMF), the Heck-type aryl-substituted TFPs were obtained. This regioselective coupling provides an efficient route for applications of TFP in organic synthesis.
2020, 40(10): 3327-3337
doi: 10.6023/cjoc202005050
Abstract:
Synthetic applications of the recently developed (NHC)Ni(Ⅱ) catalyzed[3+2] hydroalkenylation-rearrangement cascade (HARC) were investigated. The foundations of these highly substituted cyclopentadienes and methylene cyclopentanes formation were compared with typical cross-hydroalkenylation of alkenes and dienes. The desired cyclization products were examined as key starting materials for a range of olefin functionalization methodology, including Diels-Alder, epoxidation, ozonolysis, halogenation-rearrangement and fluorohydroxylation. The results showed that several very interesting carbon skeletons can be obtained easily with high diastereoselectivity in one step or in cascade.
Synthetic applications of the recently developed (NHC)Ni(Ⅱ) catalyzed[3+2] hydroalkenylation-rearrangement cascade (HARC) were investigated. The foundations of these highly substituted cyclopentadienes and methylene cyclopentanes formation were compared with typical cross-hydroalkenylation of alkenes and dienes. The desired cyclization products were examined as key starting materials for a range of olefin functionalization methodology, including Diels-Alder, epoxidation, ozonolysis, halogenation-rearrangement and fluorohydroxylation. The results showed that several very interesting carbon skeletons can be obtained easily with high diastereoselectivity in one step or in cascade.
2020, 40(10): 3354-3361
doi: 10.6023/cjoc202005062
Abstract:
1, 2-Diiodoalkenes can be used as precursors for synthesis of functional molecules such as heterocyclic drugs and organic conjugated materials due to their derivability of functional groups. Herein, alkynes can be converted into 1, 2-trans-diiodioalkenes efficiently and conveniently by using inexpensive and stable sodium iodide as iodine source and air as oxidant under the visible-light (blue light) with normal temperature and atmospheric pressure. The corresponding reactions were operated under mild conditions with inexpensive and easily accessible reagents, which obviate the need of transition-metal-catalysts or oxidizing reagents. Meanwhile, this method is compatible with a wide range of substrates, including terminal and internal alkynes even the peptide and carbohydrates containing a variety of heteroatoms and active hydrogen.
1, 2-Diiodoalkenes can be used as precursors for synthesis of functional molecules such as heterocyclic drugs and organic conjugated materials due to their derivability of functional groups. Herein, alkynes can be converted into 1, 2-trans-diiodioalkenes efficiently and conveniently by using inexpensive and stable sodium iodide as iodine source and air as oxidant under the visible-light (blue light) with normal temperature and atmospheric pressure. The corresponding reactions were operated under mild conditions with inexpensive and easily accessible reagents, which obviate the need of transition-metal-catalysts or oxidizing reagents. Meanwhile, this method is compatible with a wide range of substrates, including terminal and internal alkynes even the peptide and carbohydrates containing a variety of heteroatoms and active hydrogen.
2020, 40(10): 3399-3409
doi: 10.6023/cjoc202006007
Abstract:
Pd-catalyzed allylic alkylation reaction of α-substituted benzyl nitriles with branched allyl carbonates in the presence of bulkier N-heterocyclic carbene ligand was reported, which provided the corresponding allylated products in good yield with high regio- and diastereo-selectivity.
Pd-catalyzed allylic alkylation reaction of α-substituted benzyl nitriles with branched allyl carbonates in the presence of bulkier N-heterocyclic carbene ligand was reported, which provided the corresponding allylated products in good yield with high regio- and diastereo-selectivity.
2020, 40(10): 3410-3419
doi: 10.6023/cjoc202005066
Abstract:
Fluoroalkylated alkenes are of significant importance in life sciences and functional materials. The fluoroalkylation of alkynes offers an efficient method for the synthesis of functionalized fluoroalkylated alkenes. However, the current methods are often limited to 1, 2-difunctionalization, while the remote fluoroalkylative difunctionalization of alkynes has been rarely developed. Herein, a novel visible-light-induced remote halo-difluoroalkylation of thioalkynes is realized with difluoroalkyl halides as the radical source, forming distally halogenated (Z)-fluoroalkylated alkenes in moderate to high yields with excellent regio-, stereo-, and site-selectivity. The notable features of this reaction include the mild reaction conditions, broad substrate scope, concurrent formation of three new chemical bonds, and a thermodynamically less stable (Z)-alkene, thus enabling it a highly attractive method for organic synthesis. It represents a new advance on the direct C-H bond halogenation. Preliminary mechanistic studies indicate a cascade radical process involving the heteroatom-induced β-fluoroalkylation of C-C triple bonds, intramolecular 1, 5-hydrogen atom transfer (1, 5-HAT), single electron transfer (SET) oxidation and halide addition.
Fluoroalkylated alkenes are of significant importance in life sciences and functional materials. The fluoroalkylation of alkynes offers an efficient method for the synthesis of functionalized fluoroalkylated alkenes. However, the current methods are often limited to 1, 2-difunctionalization, while the remote fluoroalkylative difunctionalization of alkynes has been rarely developed. Herein, a novel visible-light-induced remote halo-difluoroalkylation of thioalkynes is realized with difluoroalkyl halides as the radical source, forming distally halogenated (Z)-fluoroalkylated alkenes in moderate to high yields with excellent regio-, stereo-, and site-selectivity. The notable features of this reaction include the mild reaction conditions, broad substrate scope, concurrent formation of three new chemical bonds, and a thermodynamically less stable (Z)-alkene, thus enabling it a highly attractive method for organic synthesis. It represents a new advance on the direct C-H bond halogenation. Preliminary mechanistic studies indicate a cascade radical process involving the heteroatom-induced β-fluoroalkylation of C-C triple bonds, intramolecular 1, 5-hydrogen atom transfer (1, 5-HAT), single electron transfer (SET) oxidation and halide addition.
2020, 40(10): 3420-3425
doi: 10.6023/cjoc202005058
Abstract:
15-Oxopuupehenoic acid is a new merosesquiterpenoid isolated in 2009 by Crews group from the crude sponge extracts prioritized a Papua New Guinea collection of Hyrtios sp. Its possible structure was deduced to be tetracyclic chromanones 1a~1b or benzo[c]oxepin-1(3H)-ones 1c~1d based on the spectra data, and later determinded to be 1a by analysis of its gHMBC correlations spectra. Recently Alvarez-Manzaneda and Chahboun group obtained 1a by chemical synthesis which spectra data did not match well with those of natural 15-oxopuupehenoic acid. We started from R-(—)-carvone and approched its possible structure 1b through a convergent coupling-cyclization strategy. Our sythesis featured Suzuki carbonylative coupling reaction and KOH promoted intramolecular cyclization reaction to construct the unique chromanone subunit. The spectra data of synthetic 1b did not match well with those of natural 15-oxopuupehenoic acid either which indicated its structure needed revision.
15-Oxopuupehenoic acid is a new merosesquiterpenoid isolated in 2009 by Crews group from the crude sponge extracts prioritized a Papua New Guinea collection of Hyrtios sp. Its possible structure was deduced to be tetracyclic chromanones 1a~1b or benzo[c]oxepin-1(3H)-ones 1c~1d based on the spectra data, and later determinded to be 1a by analysis of its gHMBC correlations spectra. Recently Alvarez-Manzaneda and Chahboun group obtained 1a by chemical synthesis which spectra data did not match well with those of natural 15-oxopuupehenoic acid. We started from R-(—)-carvone and approched its possible structure 1b through a convergent coupling-cyclization strategy. Our sythesis featured Suzuki carbonylative coupling reaction and KOH promoted intramolecular cyclization reaction to construct the unique chromanone subunit. The spectra data of synthetic 1b did not match well with those of natural 15-oxopuupehenoic acid either which indicated its structure needed revision.
2020, 40(10): 3426-3430
doi: 10.6023/cjoc202005022
Abstract:
A silver-mediated oxidative coupling reaction of arylboronic acids with fluoroform-derived AgCF3 using K2S2O8 as oxidant was developed. This reaction provides a new route to trifluoromethylated arenes.
A silver-mediated oxidative coupling reaction of arylboronic acids with fluoroform-derived AgCF3 using K2S2O8 as oxidant was developed. This reaction provides a new route to trifluoromethylated arenes.
2020, 40(10): 3431-3438
doi: 10.6023/cjoc202005001
Abstract:
As a bioisostere for phenyl rings, tert-butyl groups and internal alkynes, bicyclo[1.1.1]pentane (BCP) can improve the drug-like qualities of bioactive molecules. Therefore, the incorporation of high-value functional groups to BCP scaffold becomes an efficient synthetic strategy to design new bioisosteres in drug development. Herein a radical-mediated bromoalkylation of[1.1.1]propellane was disclosed, leading to brominated BCP derivatives. Bromoalkyl heteroarylsulfones were employed as dual-function reagents in the radical transformation, in which two functionalities, alkylheteroarylsulfone and bromine atom, were concurrently introduced into[1.1.1]propellane. These reactions proceeded rapidly, and were generally completed within 2 h at room temperature. A variety of new alkylheteroarylsulfone-substituted BCP derivatives were furnished with high product diversity. This protocol features excellent atom-economy, simple operation, and gram-scale preparation.
As a bioisostere for phenyl rings, tert-butyl groups and internal alkynes, bicyclo[1.1.1]pentane (BCP) can improve the drug-like qualities of bioactive molecules. Therefore, the incorporation of high-value functional groups to BCP scaffold becomes an efficient synthetic strategy to design new bioisosteres in drug development. Herein a radical-mediated bromoalkylation of[1.1.1]propellane was disclosed, leading to brominated BCP derivatives. Bromoalkyl heteroarylsulfones were employed as dual-function reagents in the radical transformation, in which two functionalities, alkylheteroarylsulfone and bromine atom, were concurrently introduced into[1.1.1]propellane. These reactions proceeded rapidly, and were generally completed within 2 h at room temperature. A variety of new alkylheteroarylsulfone-substituted BCP derivatives were furnished with high product diversity. This protocol features excellent atom-economy, simple operation, and gram-scale preparation.
2020, 40(10): 3439-3445
doi: 10.6023/cjoc202004052
Abstract:
A new approach to the synthesis of acteoside, a prototypical phenylpropanoid glycoside with a variety of biological activities, has been developed. The synthesis employed a regioselective glycosylation as a key step, in which a gold(I)-catalyzed glycosylation of p-tolyl 6-O-acetyl-1-thio-β-D-glucopyranoside with peracetyl L-rhamnopyranosyl ortho-alkynylbenzoate led to the desired α-(1→3) linked disaccharide 7-1 in a satisfactory yield. The resultant disaccharide was converted into the corresponding ortho-alkynylbenzoate donor and subjected to glycosylation with aglycone, subsequent deprotection of the protecting groups furnished acteoside.
A new approach to the synthesis of acteoside, a prototypical phenylpropanoid glycoside with a variety of biological activities, has been developed. The synthesis employed a regioselective glycosylation as a key step, in which a gold(I)-catalyzed glycosylation of p-tolyl 6-O-acetyl-1-thio-β-D-glucopyranoside with peracetyl L-rhamnopyranosyl ortho-alkynylbenzoate led to the desired α-(1→3) linked disaccharide 7-1 in a satisfactory yield. The resultant disaccharide was converted into the corresponding ortho-alkynylbenzoate donor and subjected to glycosylation with aglycone, subsequent deprotection of the protecting groups furnished acteoside.
2020, 40(10): 3446-3451
doi: 10.6023/cjoc202004015
Abstract:
An efficient conversion of quinolines to 1, 2-dihydroquinolines (50%~96% yield) was developed via the modification of the known methods. It was found that using sodium cyanoborohydride as a reductant would overcome the low conversion often encountered in previous studies. A series of N-alkoxycarbonyl-1, 2-dihydroquinolines were obtained through reduction of activated quinolium salts. Notably, with the exception of the 3-and 4-substituted substrates, a mixture of 1, 2-dihydro-quinolines and the over reduced tetrahydroquinolines was obtained with the ratio over 4:1. Besides, compared to the established methods, an easy operation without using large excess of chloroformate further enhances practicability of the methodology.
An efficient conversion of quinolines to 1, 2-dihydroquinolines (50%~96% yield) was developed via the modification of the known methods. It was found that using sodium cyanoborohydride as a reductant would overcome the low conversion often encountered in previous studies. A series of N-alkoxycarbonyl-1, 2-dihydroquinolines were obtained through reduction of activated quinolium salts. Notably, with the exception of the 3-and 4-substituted substrates, a mixture of 1, 2-dihydro-quinolines and the over reduced tetrahydroquinolines was obtained with the ratio over 4:1. Besides, compared to the established methods, an easy operation without using large excess of chloroformate further enhances practicability of the methodology.
2020, 40(10): 3452-3462
doi: 10.6023/cjoc202003005
Abstract:
Using cinchona-derived bifunctional squaramides as catalyst, an asymmetric addition of aurone-derived azadienes with pyrazolin-5-ones was developed, providing a series of chiral triarylmethanes bearing pyrazole moiety with up to 99% ee.
Using cinchona-derived bifunctional squaramides as catalyst, an asymmetric addition of aurone-derived azadienes with pyrazolin-5-ones was developed, providing a series of chiral triarylmethanes bearing pyrazole moiety with up to 99% ee.
2020, 40(10): 3463-3466
doi: 10.6023/cjoc202005085
Abstract:
Amines are important intermediates in organic synthesis. The hydrosilylation of imines provides a convenient method for the synthesis of amines. Transition metal and main group catalysts have been widely applied in the hydrosilylation of imines. However, it would be more practical to use simpler reaction conditions to realize such reactions. In this paper, a fast hydrosilylation of aldimine was realized by using cheap t-BuOK as the promoter, providing an efficient method for the synthesis of amines in high yield. This reaction features rapid reaction, facile conditions, and robust practicability.
Amines are important intermediates in organic synthesis. The hydrosilylation of imines provides a convenient method for the synthesis of amines. Transition metal and main group catalysts have been widely applied in the hydrosilylation of imines. However, it would be more practical to use simpler reaction conditions to realize such reactions. In this paper, a fast hydrosilylation of aldimine was realized by using cheap t-BuOK as the promoter, providing an efficient method for the synthesis of amines in high yield. This reaction features rapid reaction, facile conditions, and robust practicability.
2020, 40(10): 3467-3470
doi: 10.6023/cjoc202005091
Abstract:
By overexpressing the positive regulatory gene, the silent gene cluster tjh in Streptomyces aureus SP-371 was successfully activated. The mutant strain could produce compounds with two distinct core strucutures which are pentacyclic and tetracyclic structures. It was speculated that these two types of skeletons might be derived from the same intermediate through two different post-modified pathways. These two tailoring pathways were intercepted by the double gene knockout, and aureuspiro was successfully accumulated in the mutant. Aureuspiro is a new natural product with a novel spiro-naphthoquinone structure. Despite aureuspiro is not a true intermediate in the biosynthesis of final products, it could support the hypothesis about structure of the common intermediate.
By overexpressing the positive regulatory gene, the silent gene cluster tjh in Streptomyces aureus SP-371 was successfully activated. The mutant strain could produce compounds with two distinct core strucutures which are pentacyclic and tetracyclic structures. It was speculated that these two types of skeletons might be derived from the same intermediate through two different post-modified pathways. These two tailoring pathways were intercepted by the double gene knockout, and aureuspiro was successfully accumulated in the mutant. Aureuspiro is a new natural product with a novel spiro-naphthoquinone structure. Despite aureuspiro is not a true intermediate in the biosynthesis of final products, it could support the hypothesis about structure of the common intermediate.
2020, 40(10): 3471-3472
doi: 10.6023/cjoc202000064
Abstract:
Transition Metal-Catalyzed Cross-Coupling of Carbene from Ketones or Aldehydes via N-Tosylhydrazones
2020, 40(10): 3473-3474
doi: 10.6023/cjoc202000065
Abstract:
2020, 40(10): 3475-3477
doi: 10.6023/cjoc202000066
Abstract:
2020, 40(10): 3478-3480
doi: 10.6023/cjoc202000067
Abstract:
2020, 40(10): 3481-3482
doi: 10.6023/cjoc202000068
Abstract:
2020, 40(10): 3483-3484
doi: 10.6023/cjoc202000069
Abstract:
2020, 40(10): 3485-3486
doi: 10.6023/cjoc202000070
Abstract:
2020, 40(10): 3487-3489
doi: 10.6023/cjoc202000071
Abstract:
2020, 40(10): 3490-3491
doi: 10.6023/cjoc202000072
Abstract:
