Asymmetric Catalytic System Research Articles

Synthesis of Functionalized Cycloheptadienones Starting from Phenols and Using a Rhodium/Boron Asymmetric Catalytic System.

Skeletal editing offers a unique route to assemble complex architectures from simple feedstocks that are otherwise difficult to obtain. However, the asymmetric version of skeletal editing has not been widely studied. Herein, we present a modular rhodium/boron asymmetric catalytic system that enables ring-expansion of phenols with cyclopropenes to synthesize highly functionalized cycloheptadienones in excellent chemo- and regioselectivities. This unique protocol features with low-catalyst loading, atom and step-economies, and mild neutral reaction conditions. Isotope-labelling experiments and DFT calculations have been conducted to reveal that boron reagent plays a vital role in the whole catalytic cycle.

Synthesis of Functionalized Cycloheptadienones Starting from Phenols and Using a Rhodium/Boron Asymmetric Catalytic System

Skeletal editing offers a unique route to assemble complex architectures from simple feedstocks that are otherwise difficult to obtain. However, the asymmetric version of skeletal editing has not been widely studied. Herein, we present a modular rhodium/boron asymmetric catalytic system that enables ring‐expansion of phenols with cyclopropenes to synthesize highly functionalized cycloheptadienones in excellent chemo‐ and regioselectivities. This unique protocol features with low‐catalyst loading, atom and step‐economies, and mild neutral reaction conditions. Isotope‐labelling experiments and DFT calculations have been conducted to reveal that boron reagent plays a vital role in the whole catalytic cycle.

A General Copper-Box System for the Asymmetric Arylative Functionalization of Benzylic, Propargylic or Allenylic Radicals.

Radical-involved arylative cross-coupling reactions have recently emerged as an attractive strategy to access valuable aryl-substituted motifs. However, there still exist several challenges such as limited scope of radical precursors/acceptors, and lack of general asymmetric catalytic systems, especially regarding the multicomponent variants. Herein, we reported a general copper-Box system for asymmetric three-component arylative radical cross-coupling of vinylarenes and 1,3-enynes, with oxime carbonates and aryl boronic acids. The reactions proceed under practical conditions in the absence or presence of visible-light irradiation, affording chiral 1,1-diarylalkanes, benzylic alkynes and allenes with good enantioselectivities. Mechanistic studies imply that the copper/Box complexes play a dual role in both radical generation and ensuing asymmetric cross-coupling. In the cases of 1,3-enynes, visible-light irradiation could improve the activity of copper/Box complex toward the initial radical generation, enabling better efficiency match between radical formation and cross-coupling.

Polarizability matters in enantio-selection

The prevalence of chirality, or, handedness in biological world is a fundamental phenomenon and a characteristic hallmark of life. Thus, understanding the origin of enantio-selection, i.e., the sense and magnitude of asymmetric induction, has been a long-pursued goal in asymmetric catalysis. Herein, we demonstrated a polarizability-derived electronic effect that was shown to be capable of rationalizing a broad range of stereochemical observations made in the field of asymmetric catalysis. This effect provided a consistent enantio-control model for the prediction of major enantiomers formed in a ruthenium-catalyzed asymmetric transfer hydrogenations of ketones. Direct and quantitative linear free energy relationships between substrates’ local polarizabilities and observed enantio-selectivity were also revealed in three widely known asymmetric catalytic systems covering both reductions and oxidations. This broadly applicable polarizability-based electronic effect, in conjunction with conventional wisdom mainly leveraging on steric effect considerations, should aid rational design of enantio-selective processes for better production of chiral substances.

Catalytic asymmetric carbenoid α-C-H insertion of ether.

Significant advancements have been made in catalytic asymmetric α-C-H bond functionalization of ethers via carbenoid insertion over the past decade. Effective asymmetric catalytic systems, featuring a range of chiral metal catalysts, have been established for the enantioselective synthesis of diverse ether substrates. This has led to the generation of various enantioenriched, highly functionalized oxygen-containing structural motifs, facilitating their application in the asymmetric synthesis of bioactive natural products.

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Pd‐catalyzed asymmetric allylic C—H functionalization has grown to be a general platform to access densely functionalized chiral molecules from easily available alkenes. In recent years, the adoption of asymmetric organo/palladium cooperative catalysis and building up a library of structurally tunable and bulky chiral phosphoramidite ligands have opened new avenues to create regio‐ and enantioselective Pd‐catalyzed allylic C—H functionalization reactions. Gong and coworkers describe their journey to the identification of asymmetric catalytic systems, mechanism of allylic C—H activation, control of stereo‐ and regioselectivity, and applications in asymmetric synthesis. More details are discussed in the article by Gong et al. on page 1841—1848.image

Pd‐Catalyzed Asymmetric Allylic C—H Functionalization

Comprehensive SummaryPd‐catalyzed asymmetric allylic C—H functionalization has emerged as a powerful tool to access chiral, densely functionalized molecules from easily accessible alkenes, enabling the increase of the step‐ or atom‐economy by minimizing functional group manipulations for preparing allylating reagents. Due to the inadequacy of stereoselection strategies, the asymmetric allylic C—H functionalization is still in the early stage. In this essay, we will describe our journey to identification of asymmetric catalytic systems, mechanism of allylic C—H activation, control of stereo‐ and regioselectivity, and applications in asymmetric synthesis.What is the most favorite and original chemistry developed in your research group?The establishment of asymmetric organo/transition‐metal cooperative catalysis to enable enantioselective reactions.How do you get into this specific field? Could you please share some experiences with our readers?We initially attempted to expand the chiral enamine/Pd cooperative catalysis to create asymmetric allylic C—H alkylation of α‐olefins. Although this idea turned out to be unsuccessful, we finally accomplished an asymmetric allylic C—H alkylation of allylarenes enabled by cooperative catalysis of achiral amine, chiral phosphoric acid and palladium, marking a starting point to deeply get involved in this field.How do you supervise your students?I am basically strict with students in regulation and technique, but respect them very much. They are always my co‐workers and have equal authority in chemistry if they like.What is the most important personality for scientific research?Hardworking and critical thinking always pay off. What are your hobbies? What's your favorite book(s)?I have ever enjoyed learning martial arts and playing basketball, but now enjoy reading history books.Who influences you mostly in your life?So many people influence me so much in my life, it's really hard to say who mostly does. I heard the story of Hua Loo‐Keng (Hua Luo‐Geng), an eminent mathematician, in my childhood and his legend always motivates me to keep working hard.What is your favorite journal(s)?So many journals I keep reading every day, if I have to say, J. Am. Chem. Soc. may be my favorite, because it publishes, so far, my most representative work. Of course, Chin. J. Chem. is among the favorite journals.Could you please give us some advices on improving Chinese Journal of Chemistry?Keep disseminating the journal in international community and improve the diversity in authorship and contents to make it really international.

Stereo- and Regiospecific SN2' Reaction of MBH Adducts with Isocyanoacetates: en Route to Transition-Metal-Free α-Allylation of Isocyanoacetates.

Herein, we report that under mild and transition-metal-free conditions an unprecedented and practical SN2' reaction of Morita-Baylis-Hillman adducts with isocyanoacetates takes place in a stereo- and regiospecific manner. This reaction which tolerates a wide variety of functionalities delivers transformable α-allylated isocyanoacetates in high efficiencies. Preliminary studies on the asymmetric version of this reaction indicate that ZnEt2/chiral amino alcohol combinations are an asymmetric catalytic system for this transformation, giving an enantioenriched α-allylated isocyanoacetate with a chiral quaternary carbon in a high yield.

Atroposelective Synthesis of Triaryl α‐Pyranones with 1,2‐Diaxes by N‐Heterocyclic Carbene Organocatalysis

AbstractAtropisomers bearing multiple stereogenic axes are of increasing importance to the field of material science, pharmaceuticals, and catalysis. However, the atroposelective construction of multi‐axis atropisomers remains rare and challenging, due to the intrinsical difficulties in the stereo‐control of the multiple stereogenic axes. Herein, we demonstrate a single‐step construction of a new class of 1,2‐diaxially chiral triaryl α‐pyranones by an N‐heterocyclic carbene organocatalytic asymmetric [3+3] annulation of well‐designed alkynyl acylazolium precursors and enolizable sterically hindered 2‐aryl ketones. The protocol features broad substrate scope (>50 examples), excellent stereo‐control (most cases >20 : 1 dr, up to 99.5 : 0.5 er), and potentially useful synthetic applications. The success of this reaction relies on the rational design of structurally matched reaction partners and the careful selection of the asymmetric catalytic system. DFT calculations have also been performed to discover and rationalize the origin of the high stereoselectivity of this reaction.

Atroposelective Synthesis of Triaryl α-Pyranones with 1,2-Diaxes by N-Heterocyclic Carbene Organocatalysis.

Atropisomers bearing multiple stereogenic axes are of increasing importance to the field of material science, pharmaceuticals, and catalysis. However, the atroposelective construction of multi-axis atropisomers remains rare and challenging, due to the intrinsical difficulties in the stereo-control of the multiple stereogenic axes. Herein, we demonstrate a single-step construction of a new class of 1,2-diaxially chiral triaryl α-pyranones by an N-heterocyclic carbene organocatalytic asymmetric [3+3] annulation of well-designed alkynyl acylazolium precursors and enolizable sterically hindered 2-aryl ketones. The protocol features broad substrate scope (>50 examples), excellent stereo-control (most cases >20 : 1 dr, up to 99.5 : 0.5 er), and potentially useful synthetic applications. The success of this reaction relies on the rational design of structurally matched reaction partners and the careful selection of the asymmetric catalytic system. DFT calculations have also been performed to discover and rationalize the origin of the high stereoselectivity of this reaction.

Recent Progress of Electron‐Withdrawing‐Group‐Tethered Arenes Involved Asymmetric Nucleophilic Aromatic Functionalizations

AbstractElectron‐withdrawing groups (EWG) have emerged as a powerful tool for the activation of various arenes to promote nucleophilic dearomative additions for the construction of complicated chiral cyclic structures under asymmetric catalytic systems. Nitro‐indoles, nitro‐benzofurans/benzothiophenes, and related nitro‐heteroarenes are widely applied in the reaction with various nucleophiles to construct various enantioenriched polycyclic skeletons via the asymmetric dearomatization process. Meanwhile, the electron‐deficient azo‐group and nitroso‐group are an alternative powerful tool for the activation of arenes, which enable formal nucleophilic aromatic arylations with various electrophilic aromatics to construct novel chiral biaryl atropisomers. Besides, azo‐naphthanenes are served as dipolar surrogates in the reaction with nucleophilic dipolarophiles to proceed asymmetric cycloadditions to construct chiral polycyclic skeletons. The EWG‐tethered arene has proven to be a versatile protocol for the construction of structurally diversified chiral backbones. This review summarizes the latest progress of the EWG‐tethered arenes involved asymmetric transformations under organo‐ or transition metal catalysis.magnified image

Aggregation-Induced Polarization (AIP): Optical Rotation Amplification and Adjustment of Chiral Aggregates of Folding Oligomers and Polymers.

The phenomenon of aggregation-induced polarization (AIP) was observed showing optical rotation amplification and adjustment. The relationship between optical rotations of chiral aggregates of multilayered chiral folding oligomers and polymers with water% in THF (f w) has been established accordingly. New multilayered chiral oligomers were synthesized under the asymmetric catalytic systems established by our laboratory recently. These products were well-characterized by UV-vis, NMR, and MALDI-TOF spectra. Absolute stereochemistry (enantio- and diastereochemistry) was assigned by comparison with similar asymmetric induction by the same catalyst in our previous reactions. The present AIP work can serve as a new tool to determine chiral aggregates, especially for those that cannot display emission. AIP would also complement AIE-based CPL since AIP serves as a new tool providing enhanced right- or left-hand polarized lights with individual wavelengths. It will find many applications in chemical and materials science in the future.

Selective Synthesis of Ketones and Chiral Allylic Alcohols from the Addition of Arylboronic Acids to α,β-Unsaturated Aldehydes Mediated by a Transition Metal/Monophosphorus Ligand System.

Here, we demonstrated a transition metal-mediated/monophosphorus ligand system for the selective synthesis of ketones or chiral allylic alcohols in high yields/enantiomeric excess from the 1,2-addition of arylboronic acids to α,β-unsaturated aldehydes. Notably, isomerization of the chiral allylic alcohols to ketones was suppressed by the Ru-catalyzed/monophosphorus ligand system. The asymmetric catalytic system provides an alternative and efficient method of preparing chiral allylic alcohols.

Recent Advances in Asymmetric Organomulticatalysis

AbstractAsymmetric multi‐catalysis, designed to mimic catalytic processes in nature, is a powerful instrument to fulfil fascinating transformations. As a result, this area of research has attracted considerable interests within chemistry communities. Although there are numerous reviews involving multi‐catalysis, reviews describing asymmetric organomulticatalysis remain rare. Taking into consideration that organocatalysts possess the superiorities of effortless availability, inexpensiveness, hypotoxicity, facile handling and hyposensitivity to moisture and oxygen, they have definite advantage in their own distinct modes of activation when utilized in multi‐catalytic reactions. Organomulticatalysis refers to the synthetic strategies of modular combination of organo‐catalyzed reactions into one synthetic operation with minimum workup or change in conditions. It is apparent that a variety reports utilizing the concept of enantioselective organomulticatalysis have substantially surfaced in the past few years. Hence, it is indispensable to succinctly present all such reports by means of disclosing the mechanistic analysis, as well as the challenges and issues associated in the development of the asymmetric catalytic system. Additionally, this review will introduce some of the unsettled conundrums and possible innovations in this field.magnified image

An efficient dynamic asymmetric catalytic system within a zinc-templated network.

Enhanced cooperativity leading to high catalytic activity and stereoselectivity has been achieved through a complex network of simple species interacting reversibly. This novel dynamic catalytic system relies on bipyridine-based organocatalytic ligands and zinc(ii) as the template. It demonstrates the effectiveness of dealing with mixtures rather than single species in asymmetric catalysis.

Effect of ligand sequence-specific modification on DNA hybrid catalysis.

Development of a stereoselective asymmetric catalytic system with high conversion is the key to success for acquiring chiral materials. In recent years, DNA hybrid catalysts have attracted significant interest due to their excellent abilities in accelerating reactions and achieving high enantioselectivity. We report here that bipyridine linked with polyamide as a sequence-specific catalytic ligand was designed to perform a DNA hybrid asymmetric reaction. The products presented different stereoselectivities compared to the results of reactions catalyzed by bipyridine. Comparing catalytic experiments based on alternative oligonucleotides verified that sequence-locating of the ligand affected the catalytic microenvironment. Circular dichroism spectra, combined with singular value decomposition, proposed that different binding modes could exist somewhere between the ligand and alternative sequences. The current work provides a strategy to extend the chemical range of DNA-based catalysis.

Non-Classical C–H···X Hydrogen Bonding and Its Role in Asymmetric Organocatalysis

Non-classical hydrogen bonds (NCHBs) have attracted significant interest in the past decade particularly because of their important role in asymmetric catalytic systems. These weak interactions ( 1 Introduction 2 Hydrogen Bonds (HBs) and Non-Classical Hydrogen Bonds (NCHBs) 3 Early Developments in NCHBs 4 Selected Examples of NCHBs in Organic Transformations 5 Recent Examples of NCHBs in Enantioselective Reactions 6 Conclusions and Outlook

ChemInform Abstract: Recent Advances in Asymmetric Counteranion‐Directed Catalysis (ACDC).

AbstractReview: 45 refs.

Recent Advances in Asymmetric Counteranion‐directed Catalysis (ACDC)

AbstractAs expected, chemists have dedicated efforts in the development of asymmetric catalytic reactions based on lessons from nature. The decisive presence of the chiral anions in many natural chiral catalysts inspires the design of new asymmetric catalytic systems based on them. Thus, in this Minireview the recent contributions of asymmetric counteranion‐directed catalysis (ACDC) are reported. Discussions about development of new concepts, designed of catalysis and application of them in different reactions also are exposed.

Silicone‐Supported Cinchona Alkaloid Derivatives as Insoluble Organocatalysts in the Enantioselective Dimerization of Ketenes

AbstractA straightforward procedure is presented for the covalentimmobilization of ester and silyl ether derivatives of theCinchona alkaloid 10,11‐dihydroquinidine within insoluble cross‐linked silicone elastomeric films. These materials were effective heterogeneous organocatalysts in the asymmetric dimerization of ketenes, which provided chiral Weinreb β‐ketoamides in 28–83 % yield and 79–99 % ee in the course of several recycles. A productivity/enantioselectivity protocol is also proposed to better assess the relative merits of soluble and supported asymmetric catalytic systems towards process intensification.