Introduction of the trifluoromethyl group (CF3) into organic molecules in an enantioselective manner has attracted significant attention, but still remains a challenging problem. We herein report a ...catalytic asymmetric trifluoromethylation of cyclic ketones via a ScIII/chiral bisoxazoline‐catalyzed homologation reaction by employing 2,2,2‐trifluorodiazoethane (CF3CHN2) as the CF3 source. This desymmetrization process is highly efficient and generates two chiral centers with excellent diastereoselectivity and enantioselectivity, affording chiral α‐trifluoromethyl cyclic ketones in a straightforward manner.
α‐Trifluoromethyl cycloheptanones containing the C(sp3)−CF3 bond on the chiral centers were accessed through a highly stereoselective ScIII/chiral bisoxazoline‐catalyzed homologation reaction of cyclic ketones with CF3CHN2 as the trifluoromethylation reagent. This reaction could be applied to construct silicon‐stereogenic centers with moderate diastereoselectivities and high enantioselectivities.
Triggered by the endogenous chemical energy in the tumor microenvironment (TME), chemodynamic therapy (CDT) as an emerging non‐exogenous stimulant therapeutic modality has received increasing ...attention in recent years. The chemodynamic agents can convert internal hydrogen peroxide (H2O2) into the lethal reactive oxygen species (ROS) hydroxyl radicals (•OH) for oncotherapy. Compared with other therapeutic modalities, CDT possesses many notable advantages, such as tumor‐specific, highly selective, fewer systemic side effects, and no need for external stimulation. Nevertheless, mild acid pH, low H2O2 content, and overexpressed reducing substance in TME severely suppressed the CDT efficiency. With the rapid development of nanotechnology, some kinds of nanomaterials have been utilized with improved CDT efficiency. In particular, the excellent photo‐, ultrasound‐, magnetic‐, and other stimuli‐response properties of nanomaterials make it possible for combination cancer therapy of CDT with other therapeutic modalities, and it has shown superior anti‐cancer activity than monotherapies. Therefore, it is necessary to summarize the application of nanomaterial‐based chemodynamic cancer therapy. In this review, the various nanomaterials‐based nanoplatforms for CDT and its combinational therapies are summarized and discussed, aiming to provide inspiration for the design of better‐quality agents to promote the CDT development and lay the foundation for its future conversion to clinical applications.
Chemodynamic therapy (CDT) is an emerging non‐exogenous stimulant therapeutic modality and has drawn increasing attention in recent years. In particular, varieties of nanomaterials have been utilized in CDT with encouraging therapeutic efficiency. The latest progress on CDT‐involved combined therapy is overviewed, aiming to provide inspiration for the design of better‐quality agents and hoping to promote CDT future clinical conversion.
This Review summarizes the development of catalytic asymmetric dearomatization (CADA) reactions. The CADA reactions discussed herein include oxidative dearomatization reactions, dearomatization by ...Diels–Alder and related reactions, the alkylative dearomatization of electron‐rich arenes, transition‐metal‐catalyzed dearomatization reactions, cascade sequences involving asymmetric dearomatization as the key step, and nucleophilic dearomatization reactions of pyridinium derivatives. Asymmetric dearomatization reactions with chiral auxiliaries and catalytic asymmetric reactions of dearomatized substrates are also briefly introduced. This Review intends to provide a concept for catalytic asymmetric dearomatization.
Breaking up the party: Arenes can be transformed efficiently into enantiomerically enriched, versatile ring systems by catalytic asymmetric dearomatization reactions. Known reaction types include oxidative dearomatization, dearomatization by Diels—Alder reactions, alkylative dearomatization of electron‐rich arenes, transition‐metal‐catalyzed dearomatization reactions (see example), and cascade reaction sequences involving asymmetric dearomatization as the key step.
The first copper‐catalyzed intermolecular asymmetric propargylic dearomatization/annulation cascade sequence of indoles via a copper‐allenylidene amphiphilic intermediate has been achieved. This ...protocol provides a direct asymmetric synthetic method for the preparation of tetrahydro‐5H‐indolo2,3‐bquinolines, the core structure of indole alkaloids communesins A–H and perophoramidine. This method features excellent yields, high diastereoselectivity (up to >19:1 d.r.) and enantioselectivity (up to 94 % ee), mild conditions and wide substrate scope.
Reaching great heights: The first copper‐catalyzed intermolecular asymmetric propargylic dearomatization/annulation cascade sequence of indoles via a copper‐allenylidene amphiphilic intermediate has been achieved. This protocol provides a direct asymmetric synthetic method for the preparation of tetrahydro‐5H‐indolo2,3‐bquinolines, the core structure of indole alkaloids communesins A–H and perophoramidine. This method features excellent yields, high diastereoselectivity (up to >19:1 d.r.) and enantioselectivity (up to 94 % ee), mild conditions and wide substrate scope.
Organocatalytic methods have achieved spectacular advancements for the preparation of chiral molecules in highly enantioenriched forms. The fast development of this field can mainly be attributed to ...the evolution of general and reliable activation modes. The discovery and identification of new activation modes are therefore highly desirable to push the boundaries of asymmetric reactions. In this Minireview, recent advances in enantioselective carbonyl catalysis, one useful subbranch of organocatalysis for the efficient activation of simple amines, will be summarized. With elegantly designed chiral aldehyde catalysts, highly enantioselective and efficient asymmetric reactions can be developed. Continued development of enantioselective carbonyl catalysis is expected in the future.
Highly efficient organocatalysis: Enantioselective carbonyl catalysis has become one useful subbranch of organocatalysis and has proved to be very efficient for the activation of simple amines. In this Minireview, recent advances in enantioselective carbonyl catalysis will be discussed.
Conspectus The Pictet–Spengler reaction is a fundamental named reaction in organic chemistry, and it is the most straightforward method for the synthesis of tetrahydro-β-carbolines, a core structure ...embedded in numerous alkaloids. Spiroindolenines are often proposed as possible intermediates in Pictet–Spengler reactions. However, whether the spiroindolenine species is an intermediate in the mechanism of the asymmetric Pictet–Spengler reaction remains unclear. Questions about the role of the spiroindolenine species regarding the mechanism include the following: Can the spiroindolenine species be formed effectively under Pictet–Spengler conditions? If so, what is its fate? Is the delivery of the enantioenriched tetrahydro-β-carboline product related to the spiroindolenine intermediate? Previous studies regarding these questions have not reached a consensus. Therefore, elucidating these questions will advance the field of synthetic organic chemistry. The first highly enantioselective synthesis of spiroindolenines that have the same molecular scaffold as the proposed key intermediate of the Pictet–Spengler reaction was accomplished by an Ir-catalyzed intramolecular asymmetric allylic substitution reaction of an indol-3-yl allylic carbonate. In this reaction, a piperidine, pyrrolidine, or cyclopentane ring can be introduced in conjunction with the indolenine structure. Spiroindolenines were found to undergo ring-expansive migration reactions when treated with a catalytic amount of an acid, leading to tetrahydro-β-carbolines or related tetrahydrocarbazoles. Comprehensive DFT calculations and Born–Oppenheimer molecular dynamics simulations have provided insight into the mechanism of the migration process. It has been found that the stereochemistry is strongly correlated with the electronic properties of the migratory group along with the acidity of the catalyst. Close interactions between the positively charged migratory group and the electron-rich indole ring favor the stereospecificity of the migration. Furthermore, a continuous mechanistic spectrum of the Pictet–Spengler reactions can be obtained on the basis of two readily accessible energetic parameters that are derived from computed energies for competing transition states relative to a key intermediate species. This theoretical model provides a unified mechanistic understanding of the asymmetric Pictet–Spengler reaction, which has been further supported by rationally designed prototype reactions. Chemically and stereochemically controllable migration can be achieved when multiple potential migratory groups are available. The reactivity of spiroindolenines has also been explored beyond Pictet–Spengler reactions. A one-pot Ir-catalyzed asymmetric allylic dearomatization/stereoconvergent migration allows the facile synthesis of enantioenriched tetrahydro-β-carbolines from racemic starting materials. An unprecedented six- to seven-membered ring-expansive migration can be achieved when a vinyliminium moiety is involved as a highly reactive migratory group. This reaction facilitates the stereoselective synthesis of thermodynamically challenging indole-annulated seven-membered rings. It has also been found that the migration process can be interrupted. The electrophilic migratory group released from the retro-Mannich reaction of a spiroindolenine can be captured by an inter- or intramolecular nucleophile, thus providing new entries into structurally diverse polycyclic indole derivatives. Therefore, the mechanism of the Pictet–Spengler reaction can be probed by manipulating the reactivity of the spiroindolenine species. In turn, the mechanistic insights gained herein will aid in chemical transformations toward various target molecules. This study serves as a vivid example of the positive interplay between experimental and theoretical investigations in synthetic organic chemistry.
A desymmetrization strategy was developed involving iridium‐catalyzed allylic dearomatization of indoles. The six‐membered‐ring spiroindolenines contain three contiguous stereogenic centers, ...including an all‐carbon quaternary center, and were obtained in up to 99 % yield with 99 % ee and >95:5 d.r. When treated with a catalytic amount of tosylic acid, six‐membered spiroindolenine undergoes an unprecedented six‐to‐seven‐membered ring expansion, affording the corresponding hexahydroazepino4,5‐bindole.
The Legend of Spiro: An iridium‐catalyzed desymmetrization reaction involving allylic dearomatization of indoles was developed. The six‐membered‐ring spiroindolenines were obtained in up to 99 % yield with 99 % ee and >95:5 d.r. When treated with a catalytic amount of tosylic acid, six‐membered spiroindolenine undergoes six‐to‐seven‐membered ring expansion, yielding hexahydroazepino4,5‐bindole.
An iridium‐catalyzed intramolecular asymmetric allylic dearomatization reaction of naphthol derivatives is described. Challenges confronted in this reaction include chemoselectivity between carbon ...and oxygen atoms as nucleophilic centers, diastereoselectivity when contiguous chiral centers are generated, and enantioselective control for constructing an all‐carbon quaternary stereocenter. In the presence of an iridium catalyst generated from {Ir(dbcot)Cl}2 (dbcot=dibenzocyclooctatetraene) and a new THQphos (tetrahydroquinolinedinaphthophosphoramidite) ligand, various spironaphthalenones were obtained with up to greater than 95:5 C/O selectivity, greater than 95:5 d.r., and 99 % ee, thus providing a general method for the dearomatization of naphthols.
Triple challenge: The challenges addressed in the title reaction include chemoselectivity between C and O as nucleophiles, diastereoselectivity when contiguous chiral centers are generated, and enantioselective control for constructing an all‐carbon quaternary stereocenter. The {Ir(dbcot)Cl}2/(S,Sa)‐L system leads to a general method for the dearomatization of naphthols. dbcot=dibenzocyclooctatetraene.
Van der Waals heterostructures designed by assembling isolated two‐dimensional (2D) crystals have emerged as a new class of artificial materials with interesting and unusual physical properties. ...Here, the multilayer MoS2–WS2 heterostructures with different configurations are reported and their optoelectronic properties are studied. It is shown that the new heterostructured material possesses new functionalities and superior electrical and optoelectronic properties that far exceed the one for their constituents, MoS2 or WS2. The vertical transistor exhibits a novel rectifying and bipolar behavior, and can also act as photovoltaic cell and self‐driven photodetector with photo‐switching ratio exceeding 103. The planar device also exhibits high field‐effect ON/OFF ratio (>105), high electron mobility of 65 cm2/Vs, and high photoresponsivity of 1.42 A/W compared to that in isolated multilayer MoS2 or WS2 nanoflake transistors. The results suggest that formation of MoS2–WS2 heterostructures could significantly enhance the performance of optoelectronic devices, thus open up possibilities for future nanoelectronic, photovoltaic, and optoelectronic applications.
Newly designed MoS
2
–WS
2
heterostructures perform novel and enhanced optoelectronic performances. Vertical transistors possess new functionalities such as rectifying, bipolarity, photovoltaic effect, and self‐driven photodetection. Planar devices exhibit superior optoelectronic properties with high field‐effect ON/OFF ratio (>105), electron mobility of 65 cm2/Vs, and photoresponsivity of 1.42 A/W that far exceed the one for their constituents MoS2 or WS2.