Photo‐Organocatalytic Enantioselective Radical Cascade Reactions of Unactivated Olefins

Radical cascade processes are invaluable for their ability to rapidly construct complex chiral molecules from simple substrates. However, implementing catalytic asymmetric variants is difficult. Reported herein is a visible‐light‐mediated organocatalytic strategy that exploits the excited‐state reactivity of chiral iminium ions to trigger radical cascade reactions with high enantioselectivity. By combining two sequential radical‐based bond‐forming events, the method converts unactivated olefins and α,β‐unsaturated aldehydes into chiral adducts in a single step. The implementation of an asymmetric three‐component radical cascade further demonstrates the complexity‐generating power of this photochemical strategy.     

Periodic Mesoporous Organosilicas as Efficient Nanoreactors in Cascade Reactions Preparing Cyclopropanic Derivatives

In this work, three organosilica precursors functionalized with carbamate moieties were synthesized by condensing of 3‐isocyanatopropyltriethoxysilane and coupling regents of either hydroquinone (HQ), bisphenol A (BPA), or 1,1′‐bi‐2‐naphthol (BN). These organosilica precursors were covalently bonded in the framework of periodic mesoporous organosilicas by co‐condensation and hydrolysis with tetraethyl orthosilicate (TEOS) under hydrothermal treatment. The compositions and physical properties were characterized with FTIR, XRD, thermogravimetric/differential thermal analysis (TG/DTA), ²⁹Si NMR, ¹³C NMR spectroscopies, SEM, TEM, and BET technologies. These characterizations suggest that three different structures were formed as the result of different sizes and compositions of the organosilica precursors. The three mesoporous organosilicas were applied as heterogeneous catalysts in the one‐pot cascade Knoevenagel and Michael cyclopropanic reactions for the synthesis of cyclopropanic derivatives and showed excellent activity and selectivity. The highest conversion was obtained with mesoporous catalyst (MC)‐HQ owing to its ordered mesostructure, highest surface area, and weakest stereo effect of the organic linking groups compared with MC‐BAP and MC‐BN. This methodology employed cheaper and more easily obtainable raw materials as reagents over the traditional alkene additive system and these heterogeneous catalysts exhibit superior performance and recyclability than typical homogeneous organic catalysts.     

A Cascade‐Reaction Nanoreactor Composed of a Bifunctional Molecularly Imprinted Polymer that Contains Pt Nanoparticles

This study was aimed at addressing the present challenge of cascade reactions, namely, how to furnish the catalysts with desired and hierarchical catalytic ability. This issue was addressed by constructing a cascade‐reaction nanoreactor made of a bifunctional molecularly imprinted polymer containing acidic catalytic sites and Pt nanoparticles. The acidic catalytic sites within the imprinted polymer allowed one specified reaction, whereas the encapsulated Pt nanoparticles were responsible for another coupled reaction. To that end, the unique imprinted polymer was fabricated by using two well‐coupled templates, that is, 4‐nitrophenyl acetate and 4‐nitrophenol. The catalytic hydrolysis of the former compound at the acidic catalytic sites led to the formation of the latter compound, which was further reduced by the encapsulated Pt nanoparticles to 4‐aminophenol. Therefore, this nanoreactor demonstrated a catalytic‐cascade ability. This protocol opens up the opportunity to develop functional catalysts for complicated chemical processes.     

Organocatalytic Cascade Reactions: Towards the Diversification of Hydroisochromenes and Chromenes through Two Different Activation Modes

The organocatalytic enantioselective syntheses of functionalized hydroisochromenes and chromenes by trienamine‐mediated [4+2]‐cycloaddition/nucleophilic ring‐closing and iminium‐ion/aminal‐mediated oxa‐Michael/Michael/nucleophilic ring‐closing with 2‐nitroallylic alcohols are presented. The corresponding cycloadducts, with up to five stereocenters, are formed in good yield and excellent enantioselectivities. The synthetic applications of the obtained products have been demonstrated.     

Straightforward Access to the Nitric Oxide Donor Azasydnone Scaffold by Cascade Reactions of Amines

A novel one-pot cascade method for the assembly of valuable NO-donor azasydnone scaffold has been developed. The construction strategy involves a diazotization/azo coupling/elimination/double rearrangement cascade sequence of readily available amines. The current protocol enables the generation of a diverse array of azasydnones, including previously hardly accessible heteroaryl substituted azasydnones (25 examples, 70–97 % yield) with a good functional group tolerance under very mild conditions. Preliminary NO-releasing studies revealed an ability of azasydnones to produce NO in a wide range of concentrations. This method provides a new approach to nitrogen-oxygen heterocycles with potential applications in medicine and material science.     

Highly Mesoporous Metal‐Organic Frameworks as Synergistic Multimodal Catalytic Platforms for Divergent Cascade Reactions

Rational engineering and assimilation of diverse chemo‐ and biocatalytic functionalities in a single nanostructure is highly desired for efficient multistep chemical reactions but has so far remained elusive. Here, we design and synthesize multimodal catalytic nanoreactors (MCNRs) based on a mesoporous metal‐organic framework (MOF). The MCNRs consist of customizable metal nanocrystals and stably anchored enzymes in the mesopores, as well as coordinatively unsaturated cationic metal MOF nodes, all within a single nanoreactor space. The highly intimate and diverse catalytic mesoporous microenvironments and facile accessibility to the active site in the MCNR enables the cooperative and synergistic participation from different chemo‐ and biocatalytic components. This was shown by one‐pot multistep cascade reactions involving a heterogeneous catalytic nitroaldol reaction followed by a [Pd/lipase]‐catalyzed chemoenzymatic dynamic kinetic resolution to yield optically pure (>99 % ee) nitroalcohol derivatives in quantitative yields.     

Polymersomes as protocellular constructs

Despite the rapidly growing amount of knowledge on the structure and function of cells, they remain a distant bottom‐up synthetic target due to their overwhelming complexity. A path to this goal is the development of protocellular systems that approximate one or more aspects of a natural cell. Polymer vesicles, or polymersomes, are an attractive scaffold for protocellular constructs, due to our ability to engineer the polymer membrane and generate a wide range of properties. This article summarizes the current state of polymersome science with respect to the properties and functions that lend these polymer‐based systems to applications in synthetic cell research. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55, 3817–3825     

Cascade Reactions: A Driving Force in Akuammiline Alkaloid Total Synthesis

The akuammiline alkaloids are a family of intricate natural products which have received considerable attention from scientists worldwide. Despite the fact that many members of this alkaloid class were discovered over 50 years ago, synthetic chemistry has been unable to address their architectures until recently. This minireview provides a brief overview of the rich history of the akuammiline alkaloids, including their isolation, structural features, biological activity, and proposed biosyntheses. Furthermore, several recently completed total syntheses are discussed in detail. These examples not only serve to highlight modern achievements in alkaloid total synthesis, but also demonstrate how the molecular scaffolds of the akuammilines have provided inspiration for the discovery and implementation of innovative cascade reactions for the rapid assembly of complex structures.     

Characterization of Key Intermediates in a Complex Organocatalytic Cascade Reaction Using Mass Spectrometry

Chemical scrabble : Mechanistic studies of complex organocatalytic cascade reactions are challenging owing to the presence of many species involved. Electrospray ionization mass spectrometry provides details about a one‐pot quadruple organocatalytic cascade reaction, and allows detailed characterization of the reaction and its key intermediates.

     

Bioinspired Synthesis of (+)‐Cinchonidine Using Cascade Reactions

The development of efficient syntheses of complex natural products has long been a major challenge in synthetic chemistry. Designing cascade reactions and employing bioinspired transformations are an important and reliable means of achieving this goal. Presented here is a combination of these two strategies, which allow efficient asymmetric synthesis of the cinchona alkaloid (+)‐cinchonidine. The key steps of this synthesis are a controllable, visible‐light‐induced photoredox radical cascade reaction to efficiently access the tetracyclic monoterpenoid indole alkaloid core, as well as a practical biomimetic cascade rearrangement for the indole to quinoline transformation. The use of stereoselective chemical transformations in this work makes it an efficient synthesis of (+)‐cinchonidine.     

Tunable Cascade Reactions of Alkynols with Alkynes under Combined Sc(OTf)3 and Rhodium Catalysis

Two tunable cascade reactions of alkynols and alkynes have been developed by combining Sc(OTf)₃ and rhodium catalysis. In the absence of H₂O, an endo‐cycloisomerization/C? H activation cascade reaction provided 2,3‐dihydronaphtho[1,2‐b]furans in good to high yields. In the presence of H₂O, the product of alkynol hydration underwent an addition/C? H activation cascade reaction with an alkyne, which led to the formation of 4,5‐dihydro‐3H‐spiro[furan‐2,1′‐isochromene] derivatives in good yields under mild reaction conditions. Mechanistic studies of the cascade reactions indicated that the rate‐determining step involves C? H bond cleavage and that the hydration of the alkynol plays a key role in switching between the two reaction pathways.     

Construction of Cyclobutanes by Multicomponent Cascade Reactions in Homogeneous Solution through Visible-Light Catalysis

[2+2] Photocycloaddition of two olefins is a general method to assemble the core scaffold, cyclobutane, found in numerous bioactive molecules. A new approach to synthesize cyclobutanes through multicomponent cascade reactions by merging aldol reaction and Witting reaction with visible-light-induced [2+2] cycloaddition is reported. An array of cyclobutanes with high selectivity has been achieved from commercially available aldehydes, ketones (or phosphorus ylide), and olefins with visible-light irradiation of a catalytic amount of (fac-tris(2-phenylpyridinato-C₂,N)iridium) ([Ir(ppy)₃]) at room temperature. Control experiments and spectroscopic studies revealed that the triplet–triplet energy transfer from the excited [Ir(ppy)₃]* to enones, generated in situ from aldehyde and ketone or aldehyde and phosphorus ylide, is responsible for these simple and efficient muticomponent transformations.     

Scalable and Recyclable All‐Organic Colloidal Cascade Catalysts

We report on the synthesis of core–shell microparticles (CSMs) with an acid catalyst in the core and a base catalyst in the shell by surfactant‐free emulsion polymerization (SFEP). The organocatalytic monomers were separately copolymerized in three synthetic steps allowing the spatial separation of incompatible acid and base catalysts within the CSMs. Importantly, a protected and thermo‐decomposable sulfonate monomer was used as acid source to circumvent the neutralization of the base catalyst during shell formation, which was key to obtain stable, catalytically active CSMs. The catalysts showed excellent performance in an established one‐pot model cascade reaction in various solvents (including water), which involved an acid‐catalyzed deacetalization followed by a base‐catalyzed Knoevenagel condensation. The CSMs are easily recycled, modified, and their synthesis is scalable, making them promising candidates for organocatalytic applications.     

Advancements in Gold-Catalyzed Cascade Reactions to Access Carbocycles and Heterocycles: An Overview

This review summarizes recent developments (from 2006 to 2022) in numerous important and efficient carbo- and heterocycle generations using gold-catalyzed cascade protocols. Herein, methodologies involve selectivity, cost-effectiveness, and ease of product formation being controlled by the ligand as well as the counter anion, catalyst, substrate, and reaction conditions. Gold-catalyzed cascade reactions covered different strategies through the compilation of various approaches such as cyclization, hydroarylation, intermolecular and intramolecular cascade reactions, etc. This entitled reaction is also useful for the synthesis of spiro, fused, bridged carbo- and heterocycles.     

Preparation of Cyclobutene Acetals and Tricyclic Oxetanes through Photochemical Tandem and Cascade Reactions

We describe a photochemical reaction using two starting materials, a cyclopent‐2‐enone and an alkene, which are transformed in a controlled manner via the initial [2+2]‐photocycloaddition adducts into cyclobutene aldehydes (conveniently trapped as stable acetals) or unprecedented angular tricyclic 4:4:4 oxetane‐containing skeletons. These compounds are formed through tandem or triple cascade photochemical reaction processes, respectively. Small libraries of each compound class were prepared, thus suggesting that this photochemistry approach opens new opportunities for synthesis design and for widening molecular diversity.     

炔醇分子内环化促发的串联反应在螺杂环化合物合成中的应用

螺杂环化合物独特的立体结构和丰富的理化特性,激发了研究工作者对其高效合成方法的持续关注.炔醇在过渡金属作用下经exo-dig式分子内环化可原位形成环外烯醇醚,其作为一类高活性的C2合成子,能够与同时具有亲电和亲核特性的“双亲性底物”发生串联反应,实现螺杂环骨架的快速构建.综述了近年来炔醇分子内环化促发的串联反应在螺杂环...