Interception of Transient Allyl Radicals with Low-Valent Allylpalladium Chemistry: Tandem Pd(0/II/I)-Pd(0/II/I/II) Cycles in Photoredox/Pd Dual-Catalytic Enantioselective C(sp3)-C(sp3) Homocoupling.

We present comprehensive computational and experimental studies on the mechanism of an asymmetric photoredox/Pd dual-catalytic reductive C(sp3)-C(sp3) homocoupling of allylic electrophiles. In stark contrast to the canonical assumption that photoredox promotes bond formation via facile reductive elimination from high-valent metal-organic species, our computational analysis revealed an intriguing low-valent allylpalladium pathway that features tandem operation of Pd(0/II/I)-Pd(0/II/I/II) cycles. Specifically, we propose that (i) the photoredox/Pd system enables the in situ generation of allyl radicals from low-valent Pd(I)-allyl species, and (ii) effective interception of the fleeting allyl radical by the chiral Pd(I)-allyl species results in the formation of an enantioenriched product. Notably, the cooperation of the two pathways highlights the bifunctional role of Pd(I)-allyl species in the generation and interception of transient allyl radicals. Moreover, the mechanism implies divergent substrate-activation modes in this homocoupling reaction, suggesting a theoretical possibility for cross-coupling. Combined, the current study offers a novel mechanistic hypothesis for photoredox/Pd dual catalysis and highlights the use of low-valent allylpalladium as a means to efficiently intercept radicals for selective asymmetric bond constructions.

Catalytic Asymmetric Synthesis of Atropisomers Bearing Multiple Chiral Elements: An Emerging Field.

With the rapid development of asymmetric catalysis, the demand for the enantioselective synthesis of complex and diverse molecules with different chiral elements is increasing. Owing to the unique features of atropisomerism, the catalytic asymmetric synthesis of atropisomers has attracted a considerable interest from the chemical science community. In particular, introducing additional chiral elements, such as carbon centered chirality, heteroatomic chirality, planar chirality, and helical chirality, into atropisomers provides an opportunity to incorporate new properties into axially chiral compounds, thus expanding the potential applications of atropisomers. Thus, it is important to perform catalytic asymmetric transformations to synthesize atropisomers bearing multiple chiral elements. In spite of challenges in such transformations, in recent years, chemists have devised powerful strategies under asymmetric organocatalysis or metal catalysis, synthesizing a wide range of enantioenriched atropisomers bearing multiple chiral elements. Therefore, the catalytic asymmetric synthesis of atropisomers bearing multiple chiral elements has become an emerging field. This review summarizes the rapid progress in this field and indicates challenges, thereby promoting this field to a new horizon.

Organocatalytic Atroposelective Synthesis of Indole Derivatives Bearing Axial Chirality: Strategies and Applications.

Catalytic atroposelective syntheses of axially chiral compounds have stimulated extensive interest in multiple communities, such as synthetic chemistry, biochemistry, and materials science, because of the intriguing characteristics of atropisomerism. In particular, atropisomeric indole derivatives, which contain a kind of five-membered heterocyclic framework, are widely distributed in a number of natural alkaloids, biologically relevant compounds, chiral ligands, and chiral organocatalysts. Hence, the catalytic atroposelective synthesis of indole derivatives bearing axial chirality is of considerable importance and has become an emerging focus of research. However, there are substantial challenges associated with the atroposelective synthesis of indole derivatives, including remote ortho-substituents around the chiral axis, a lower barrier for rotation, and a weaker configurational stability than that of atropisomeric six-membered biaryls. Therefore, the development of effective strategies toward the catalytic atroposelective synthesis of indole derivatives has become an urgent task.In order to tackle these challenges and to accomplish the task, our group devised a unique strategy of designing indole-derived platform molecules and developing organocatalytic enantioselective transformations of such platform molecules to synthesize atropisomeric indole derivatives; asymmetric organocatalysis has tremendous advantages and was the research area recognized by the Nobel Prize in Chemistry in 2021. This Account summarizes our endeavors in the organocatalytic atroposelective synthesis of indole derivatives bearing axial chirality. In brief, we devised and developed a series of indole-derived platform molecules, such as indolylmethanols, (hetero)aryl indoles, oxindole-based styrenes, N-aminoindoles, and indole-based homophthalic anhydrides, by introducing different functional groups onto the indole ring to achieve new reactivity and modulate the reactive site of the indole ring. As a result, these indole-derived platform molecules possess versatile and unique reactivity and are capable of undergoing a variety of organocatalytic enantioselective transformations for preparing structurally diversified indole derivatives with axial chirality.We used these strategies to accomplish the atroposelective synthesis of plenty of indole derivatives with axial chirality, including (hetero)aryl indoles, alkene-indoles, oxindole-based styrenes, N-pyrrolylindoles, and isochromenone-indoles. In addition, we gave a thorough and detailed understanding of the designed reaction by investigating the reaction pathway and activation mode. More importantly, we studied the biological activity of some products and performed catalyst design on the basis of atropisomeric indole moieties, which are helpful for disclosing more applications of indole derivatives bearing axial chirality.In the future, the organocatalytic atroposelective synthesis of indole derivatives bearing axial chirality will indubitably remain a frontier topic in the research area of asymmetric catalysis and chiral indole chemistry despite challenging issues, for instance, the atroposelective synthesis of novel indole derivatives bearing an unconventional chiral axis, the development of atropisomeric indole derivatives into powerful catalysts or ligands, and the discovery of atroposelective indole derivatives as potent drug candidates. We hope our efforts summarized in this Account will encourage chemists worldwide to devise innovative strategies toward solving the challenging issues that remain in this field, thus promoting its development to a higher level.

Effect of Ag nanoparticle size on triboelectric nanogenerator for mechanical energy harvesting.

Triboelectric nanogenerators (TENG) are generally utilized on the grounds that they can catch low-recurrence mechanical energy from various types of movement and convert it into electricity. It has been proved that the adulteration of conductive particles in the triboelectric layer can improve its output performance, but metal nanomaterials have different properties at different scales. In this paper, the triboelectric layer of TENG is a composite film made of silver nanoparticles (AgNPs) with different particle sizes (20 nm, 50 nm, 200 nm and 500 nm) that were dispersed and mixed with two-component liquid silica gel step by step. The open circuit voltage (Voc) and short circuit current (Isc) of the 20 nm component of the AgNPs-dispersed/two-component liquid silica gel TENG(At-TENG) are 102.8 V and 4.42µA, which are higher than the result execution of the other components. Smaller size nanoparticles have more number of nanoparticles when the mass fraction is the same. AgNPs form micro-capacitance structures in the insulating polymer layer and enhance the dielectric properties of the composite films through an interfacial polarization mechanism. At-TENG can light up 53 commercial LEDs and power calculators or wristband electronic watches, proving its utility as a self-powered power source. An extensive experiment proves the advantage of small size using comparison and theoretical analysis and provides suggestions for the selection of TENG dopants.

Enantioselective Reductive Homocoupling of Allylic Acetates Enabled by Dual Photoredox/Palladium Catalysis: Access to C2-Symmetrical 1,5-Dienes.

Transition-metal-catalyzed reductive coupling reactions have emerged as powerful protocols to construct C-C bonds. However, the development of enantioselective C(sp3)-C(sp3) reductive coupling remains challenging. Herein, we report a highly regio-, diastereo-, and enantioselective reductive homocoupling of allylic acetates through cooperative palladium and photoredox catalysis using diisopropylethylamine or Hantzsch ester as a homogeneous organic reductant. This straightforward protocol enables the stereoselective construction of C(sp3)-C(sp3) bonds under mild reaction conditions. A series of C2-symmetrical chiral 1,5-dienes were easily prepared with excellent enantioselectivities (up to >99% ee), diastereoselectivities (up to >95:5 dr), and regioselectivities (up to >95:5 rr). The resultant chiral 1,5-dienes can be directly used as chiral ligands in asymmetric synthesis, and they can be also transformed into other valuable chiral ligands.

Higgs Boson Emerging from the Dark.

We propose a new nonthermal mechanism of dark matter production based on vacuum misalignment. A global X-charge asymmetry is generated at high temperatures, under which both the will-be Higgs boson and the dark matter are charged. At lower energies, the vacuum changes alignment and breaks the U(1)_{X}, leading to the emergence of the Higgs bosonand of a fraction of charge asymmetry stored in the stable dark matter relic. This mechanism can be present in a wide variety of models based on vacuum misalignment, and we demonstrate it in a composite Higgs template model, where all the necessary ingredients are naturally present. A light pseudo-scalar η is always predicted, with interesting implications for cosmology, future supernova observations and exotic Z→γη decays.

Enantioselective Allylic Alkylation with 4-Alkyl-1,4-dihydro-pyridines Enabled by Photoredox/Palladium Cocatalysis.

Highly regio- and enantioselective allylic alkylation has been achieved enabled by the merger of photoredox and palladium catalysis. In this dual catalytic process, alkyl radicals generated from 4-alkyl-1,4-dihydropyridines act as the coupling partners of the π-allyl palladium complexes. The generality of this method has been illustrated through the reaction of a variety of allyl esters with 4-alkyl-1,4-dihydropyridines. This mechanistically novel strategy expands the scope of the traditional Pd-catalyzed asymmetric allylic alkylation reaction and serves as its alternative and potential complement.

Radical Alkylation of Imines with 4-Alkyl-1,4-dihydropyridines Enabled by Photoredox/Brønsted Acid Cocatalysis.

Radical alkylation of imines with 4-alkyl-1,4-dihydropyridines cocatalyzed by iridium/ruthenium complex and Brønsted acid under visible light irradiation has been achieved. Both aldimines and ketimines can undergo this transformation. Common functional groups, such as hydroxyl groups, ester, amide, ether, cyanide, and heterocycles, can be tolerated in this reaction. A variety of structurally diverse amines (57 examples) have been produced with up to 98% isolated yields using this method.

Design and Enantioselective Construction of Axially Chiral Naphthyl-Indole Skeletons.

The first enantioselective construction of a new class of axially chiral naphthyl-indole skeletons has been established by organocatalytic asymmetric coupling reactions of 2-naphthols with 2-indolylmethanols (up to 99 % yield, 97:3 e.r.). This approach not only affords a new type of axially chiral heterobiaryl backbone, but also provides a new catalytic enantioselective strategy for constructing axially chiral biaryl scaffolds by making use of the C3-electrophilicity of 2-indolylmethanols.

Catalytic Enantioselective and Regioselective [3+3] Cycloadditions Using 2-Indolylmethanols as 3 C Building Blocks.

The first catalytic asymmetric cycloaddition using 2-indolylmethanols as 3C building blocks has been established by a chiral phosphoric acid-catalyzed enantioselective and regioselective [3+3] cycloaddition of 2-indolylmethanols with azomethine ylides, which constructed biologically important tetrahydro-γ-carboline frameworks in high yields and excellent enantioselectivities (up to 83 % yield, 99:1 e.r.). This reaction not only represents the first application of 2-indolylmethanols as 3C building blocks in catalytic asymmetric cycloadditions, but also has established an abnormal regioselectivity in indolylmethanol-involved transformations.

Gallium Bromide-Promoted Dearomative Indole Insertion in 3-Indolylmethanols: Chemoselective and (Z/E)-Selective Synthesis of 3,3'-Bisindole Derivatives.

Gallium bromide (GaBr3)-promoted dearomative indole insertion in 3-indolylmethanols has been established, which chemoselectively constructs a biologically important 3,3'-bisindole framework bearing an all-carbon quaternary center in high yields and excellent (Z)-selectivities (up to 99% yield, all >95:5 Z/E). The reaction pathway was suggested to include a tandem sequence of Michael addition/C-C bond cleavage/nucleophilic addition, wherein the strong acidity of GaBr3 played a crucial role in the key step of C-C bond cleavage. This reaction not only provides a new strategy for dearomatization of indoles, but also represents a new reaction category for 3-indolylmethanols, which involves a rarely reported late-stage C-C bond cleavage of 3-indolylmethanol derivatives. In addition, this approach also offers an efficient method for the synthesis of biologically important 3,3'-bisindole derivatives.

Brønsted acid-catalyzed regioselective reactions of 2-indolylmethanols with cyclic enaminone and anhydride leading to C3-functionalized indole derivatives.

An abnormal regioselective substitution of 2-indolylmethanols with nucleophiles such as cyclic enaminone and cyclic anhydride has been established in the presence of Brønsted acid, which efficiently afforded C3-functionalized indole derivatives with structural diversity in high yield and regiospecificity (40 examples, up to 99% yield). Using this approach, the reactivity of the C3-position of the indole was switched from nucleophilic to electrophilic, which could serve as an "umpolung" strategy in organic synthesis.

Organocatalytic asymmetric cascade reactions of 7-vinylindoles: diastereo- and enantioselective synthesis of C7-functionalized indoles.

The first catalytic asymmetric cascade reaction of 7-vinylindoles has been established by the rational design of such substrates. Cascade reactions with isatin-derived 3-indolylmethanols in the presence of a chiral phosphoric acid derivative allow the diastereo- and enantioselective synthesis of C7-functionalized indoles as well as the construction of cyclopenta[b]indole and spirooxindole frameworks (all >95:5 d.r., 94->99 % ee). This approach not only addresses the great challenge of the catalytic asymmetric synthesis of C7-functionalized indoles, but also provides an efficient method for constructing biologically important cyclopenta[b]indole and spirooxindole scaffolds with excellent optical purity. Investigation of the reaction pathway and activation mode has suggested that this cascade reaction proceeds through a vinylogous Michael addition/Friedel-Crafts process, in which dual H-bonding activation of the two reactants plays a crucial role.

Enantioselective construction of a 2,2'-bisindolylmethane scaffold via catalytic asymmetric reactions of 2-indolylmethanols with 3-alkylindoles.

A chiral phosphoric acid-catalyzed asymmetric reaction of 2-indolylmethanols with 3-alkylindoles has been established, which constructed a biologically important 2,2'-bisindolylmethane scaffold in high yields and good enantioselectivities (up to 98% yield, 94:6 er). This protocol not only provides an efficient method for constructing a 2,2'-bisindolylmethane framework in an enantioselective form, but also promotes the development of 2-indolylmethanol-involved catalytic asymmetric transformations.

Organocatalytic chemo-, (E/Z)- and enantioselective formal alkenylation of indole-derived hydroxylactams using o-hydroxystyrenes as a source of alkenyl group.

The first organocatalytic asymmetric formal alkenylation of multicyclic alcohols using non-metal-based alkenes instead of alkenyl metals as a source of an alkenyl group has been established via chiral phosphoric acid catalyzed tandem reactions. This transformation directly assembles isoindolo-ß-carboline-derived hydroxylactams with o-hydroxystyrenes via an asymmetric cascade vinylogous addition/hydrogen elimination reaction sequence, offering an easy access to functionalized chiral isoindolo-ß-carbolines with one quaternary stereogenic center in high chemo-, (E/Z)-, and enantioselectivities (up to >95:5 cr, >95:5 E/Z, 97:3 er). This approach also represents the first catalytic asymmetric formal alkenylation of isoindolo-ß-carboline-derived hydroxylactams, which provides a useful strategy for functionalization of isoindolo-ß-carbolines and synthesis of chiral isoindolo-ß-carboline derivatives. In addition, the investigation on the activating mode revealed that the hydroxyl group in o-hydroxystyrene was essentially important for generating a hydrogen-bond interaction with the catalyst. The dual activation mode of hydrogen bond and ion pair between the catalyst and the substrates cooperatively facilitated the desired formal alkenylation reaction in a chemo- and stereoselective way.

Catalytic asymmetric Povarov reaction of isatin-derived 2-azadienes with 3-vinylindoles.

The first catalytic asymmetric Povarov reaction of isatin-derived 2-azadienes with 3-vinylindoles was established in the presence of chiral phosphoric acid, which tolerates a wide range of substrates with generally excellent diastereoselectivity and good enantioselectivity (up to >95 : 5 dr, 89 : 11 er). This approach will greatly enrich the chemistry of the catalytic asymmetric Povarov reaction, in particular ketone-involved transformations. Furthermore, this protocol represents the first diastereo- and enantio-selective construction of a spiro[indolin-3,2'-quinoline] framework bearing an indole moiety. This novel type of spiro-compound not only contains two chiral centers, including one quaternary stereogenic center, but also integrates two biologically important structures of spiro[indolin-3,2'-quinoline] and indole, which may find medicinal applications after bioassay.

Enantioselective reductive allylic alkylation enabled by dual photoredox/palladium catalysis.

A dual photoredox/palladium catalyzed regio- and enantioselective reductive cross-coupling of allylic acetates with tertiary/secondary alkyl bromides has been achieved, and Hantzsch ester is used as a homogeneous organic reductant. This straightforward protocol enables the stereoselective construction of C(sp3)-C(sp3) bonds under mild reaction conditions. Mechanistic studies suggest that this reaction involves radical pathways and a chiral Pd complex enables the control of the regio- and enantioselectivities.

Enantioselective Radical SN2-Type Alkylation of Morita-Baylis-Hillman Adducts Using Dual Photoredox/Palladium Catalysis.

An enantioselective radical alkylation of 4-alkyl-1,4-dihydropyridines with Morita-Baylis-Hillman (MBH) adducts has been reported. The SN2-type products are predominant. This reaction is enabled by dual photoredox/palladium catalysis. The alkylation products are provided in good yields with good regio- and enantioselectivity. The use of Ding's spiroketal-based bis(phosphine) (SKP) ligand is crucial to achieving satisfactory regio- and enantioselectivity. The resultant α,ß-unsaturated ester can be easily reduced to a synthetically useful chiral allyl alcohol.

Visible-Light-Induced Radical Acylation of Imines with α-Ketoacids Enabled by Electron-Donor-Acceptor Complexes.

A visible-light-induced radical acylation of imines with α-ketoacids has been achieved, enabled by an electron-donor-acceptor (EDA) complex. This EDA complex-mediated process eradicates the use of a photocatalyst. Visible light is used as the sole promoter for this reaction, and CO2 is the only side product. Substrates with amide, cyanide, ester, ether, halides, and heterocycles were compatible. This radical acylation allows access structurally diverse α-amino ketones (32 examples) in up to 90% isolated yields.

Enantioselective Radical Hydroacylation of Enals with α-Ketoacids Enabled by Photoredox/Amine Cocatalysis.

A photoredox/amine-cocatalyzed enantioselective radical hydroacylation of enals with α-ketoacids is described. Acyl radicals generated from α-ketoacids act as the acylation reagent with the iminium ions. This strategy provides an efficient way to access synthetically challenging 1,4-dicarbonyl compounds in an enantioselective manner. The reactions of various enals with α-ketoacids show the generality and limitations of this method.