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Transition-metal-catalyzed asymmetric allylic substitution reactions represent a hot research topic in the field of asymmetric synthesis, with significant progress having been made. Among diverse catalysis systems, relay catalysis enables sequential activation of multiple steps in one pot and the rapid construction of multiple chiral centers, providing a simple and powerful platform for organic synthesis. Recently, relay catalysis has been successfully applied to asymmetric allylic substitution reactions, and a variety of challenging transformations have been realized. This Short Review summarizes the related progress on asymmetric allylic substitution reactions based on relay catalysis over the last decade. 1 Introduction 2 The General Transformation Model 3 Allylation Relays Further Reaction 4 Initial Reaction Relays Allylation 5 Conclusion and Outlook [ABSTRACT FROM AUTHOR]

Here, we report a strategy enabling triple switchable chemo‐, regio‐, and stereodivergence in newly developed palladium‐catalyzed cycloadditions of allenes. An asymmetric pseudo‐stereodivergent cycloaddition of allenes bearing a primary leaving group at the α‐position, where a dynamic kinetic asymmetric hydroalkoxylation of racemic unactivated allenes was the enantio‐determining step, is realized, providing four stereoisomers [(Z,R), (Z,S), (E,S), and (E,R)] containing a di‐substituted alkene scaffold and a stereogenic center. By tuning reaction conditions, a mechanistically distinctive cycloaddition is uncovered selectively with the same set of substrates. By switching the position of the leaving group of allenes, a cycloaddition involving an intermolecular O‐attack is disclosed. Diverse mechanisms of the cycloaddition reactions of allenes enable rapid access to structurally and stereochemically diverse 3,4‐dihydro‐2H‐1,4‐benzoxazines in high efficiency and selectivity. [ABSTRACT FROM AUTHOR]

Inherently chiral calix[4]arenes represent a unique type of chiral molecules with significant applications, yet their catalytic enantioselective synthesis remains largely underexplored. We report herein the catalytic enantioselective synthesis of inherently chiral calix[4]arenes through the sequential organocatalyzed enantioselective Povarov reaction and aromatizations. The chiral phosphoric acid catalyzed three‐component Povarov reaction involving amino group‐substituted calix[4]arenes, aldehydes and (di)enamides desymmetrized the prochiral calix[4]arene substrates, which was followed by various aromatization methods, resulting in a diverse array of novel quinoline‐containing calix[4]arenes with good yields and high enantioselectivities (up to 75 % yield, 99 % ee). The large‐scale enantioselective synthesis and diverse derivatizations of the chiral calix[4]arene products highlight the value of this method. Furthermore, preliminary exploration into their photophysical and chiroptical properties demonstrate the potential applications of these novel calix[4]arene molecules. [ABSTRACT FROM AUTHOR]

Palladium-catalyzed asymmetric [3+2] cycloaddition reaction of vinyl cyclopropane and electron-deficient dienes was realized. The cycloaddition reaction proceeded regioselectively on the distant C=C double bond of electron-deficient dienes, and was mainly controlled by the steric hindrance of the 5-substituent of electron-deficient dienes. Chiral multi-substituted cyclopentanes bearing three functional groups (monosubstituted alkene, conjugated ester, and cyano) and three continuous stereocenters were obtained in moderate to high yields, diastereoselectivities, and enantioselectivities. [ABSTRACT FROM AUTHOR]

A novel helical polymer (compound poly-1200) containing side chains of L-leucine was synthesized. This chiral L-leucine polymer catalyst exhibited excellent catalytic activity and stereoselectivity in Aldol reaction. Poly-1200 catalyzed Aldol reaction of cyclopentanone and 4-nitrobenzaldehyde in saturated brine solution with a high enantiomeric excess (ee) value of up to 99% and a diastereomeric selectivity (dr) value of 58/42. Furthermore, the chiral polymer catalyst could be recycled three times in the asymmetric Aldol reaction without significant loss of catalytic activity. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: The first asymmetric hydrogenation of acyclic tetrasubstituted α,β‐unsaturated amides has been achieved by using Rh/DuanPhos complex as a catalyst, delivering chiral β‐amino amides with two contiguous chiral centers in excellent yields and high enantioselectivities (up to 99% yield, 96% ee), which provides efficient and concise access to valuable β‐amino amide derivatives. The gram‐scale reaction and efficient transformation of β‐amino amide to β‐amino acid and β‐amino cyanide demonstrated the utility of this methodology. [ABSTRACT FROM AUTHOR]

The Reformatsky reagent derived from ethyl bromoacetate circumvents the challenge associated with the direct regio- and enantioselective iridium-catalyzed allylic alkylation with an unstabilized aliphatic ester enolate. Notably, this work represents the first example of using a Reformatsky reagent in a metal-allyl reaction, which permits the direct construction of enantioenriched β-stereogenic homoallylic esters without preactivation of the pronucleophile or post-reaction modification of the product (e.g., thermal decarboxylation of a 1,3-dicarbonyl). Moreover, the process allows the coupling of a broad range of sterically and electronically diverse electrophiles bearing aryl, heteroaryl and alkenyl derivatives, including the significantly more challenging alkyl-substituted allylic carbonates. The versatility of the ester product is exemplified by a series of functional group manipulations and the development of a concise and efficient enantioselective total synthesis of the natural product, (+)-descurainolide A. Finally, mechanistic studies indicate that the zinc enolate behaves as a soft nucleophile that undergoes outer-sphere alkylation. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: The first asymmetric hydrogenation of acyclic tetrasubstituted α,β‐unsaturated amides has been achieved by using Rh/DuanPhos complex as a catalyst, delivering chiral β‐amino amides with two contiguous chiral centers in excellent yields and high enantioselectivities (up to 99% yield, 96% ee), which provides efficient and concise access to valuable β‐amino amide derivatives. The gram‐scale reaction and efficient transformation of β‐amino amide to β‐amino acid and β‐amino cyanide demonstrated the utility of this methodology. [ABSTRACT FROM AUTHOR]

Carbopalladation‐initiated cascade reaction involving 1,4‐Pd migration is a straightforward and powerful approach to activate remote C─H bond, forging versatile fused polycyclic compounds containing fluorene fragment which are highly valuable synthetic targets. However, its asymmetric variants pose considerable challenges and have not been explored. Here the first asymmetric palladium‐catalyzed tandem carbopalladation is reported, 1,4‐Pd migration reaction of ortho‐iodophenol‐derived allyl ether under mild conditions, allowing the transformation of a wide range of substrates in good to excellent enantioselectivities, and providing a facile and straight forward access to tetracyclic dihydroindeno[1,2,3‐de]chromene bearing a chiral fluorene skeleton. A good functional group tolerance, high stereoselectivity, as well as the good chiroptical properties (high fluorescence quantum yields, circular dichroism) of the products make this approach highly attractive. Moreover, density functional theory (DFT) calculations indicate that the protonation of five‐membered palladacycle intermediate is more favorable rather than its direct reductive elimination process. [ABSTRACT FROM AUTHOR]

Heteroaromatic N‐oxides, renowned for their highly polar N─O bond and robust structure, exhibit significant bioactivities and have played a pivotal role in various drug development projects since the discovery of Minoxidil. Moreover, heteroaromatic N‐oxides, featuring axially chiral biaryl frameworks, are indispensable as Lewis base catalysts and ligands in organic synthesis. Despite their importance, synthesizing these chiral compounds is challenging, necessitating chiral starting materials or resolution processes. Catalytic strategies rely on the functionalization of heteroaromatic N‐oxide compounds, leading to products with a relatively limited skeletal diversity. This study introduces a Cu‐catalyzed atroposelective method for synthesizing biaryl N‐oxides via de novo heteroaromatic N‐oxide ring formation. This mild and efficient approach achieves excellent stereoselectivities (up to 99:1 er), enabling the production of a wide array of N‐oxides with novel heteroaromatic scaffolds. The axially chiral N‐oxide product 3f demonstrates high stereoselectivity and recyclability as a Lewis base catalyst. Additionally, product 3e exhibits promising therapeutic efficacy against triple‐negative breast cancer, with IC50 values of 4.8 and 5.2 µm in MDA‐MB‐231 and MDA‐MB‐468 cells, respectively. This research not only advances the synthesis of challenging chiral heteroaromatic N‐oxides but also encourages further exploration of N‐oxide entities in the discovery of bioactive small molecules. [ABSTRACT FROM AUTHOR]

This paper, for the first time, reports calculating molecular descripts from the combinations of catalysts and substrates, for enantioselectivity predictions in chiral phosphoric acid–catalyzed thiol addition to N‐acylimines. Ten molecular descriptors, together with random forest (RF) algorithm, were used to establish the quantitative structure–selectivity relationship (QSSR) model (RF Model I), yielding correlation coefficient of R=0.982, root mean square (rms) error of 0.604 kJ/mol (for 800 enantioselectivity ΔΔG from 32 catalysts in the training set), R=0.922, rms=1.075 kJ/mol (for 275 enantioselectivity ΔΔG from 11 new catalysts in the test set). The RF Model I was proved to be more accurate in enantioselectivity predictions, compared with the QSSR models reported in the literature and with the RF Model II and RF Model III in this work. Moreover, the RF Model I was based on simple Dragon descriptors and capable of extrapolative prediction for new catalysts. Therefore, it is reasonable deriving molecular descriptors from the combinations of catalysts and substrates (thiols and imines). This work provides a new method for the predictions of enantioselectivity ΔΔG. [ABSTRACT FROM AUTHOR]

A series of bis‐cyclometalated chiral‐at‐metal iridium(III) complexes containing a coordinated secondary phosphine oxide (SPO) have been synthesized and evaluated as catalysts in the asymmetric transfer hydrogenation (ATH) of acetophenone. The catalytic results show that SPO ligands have a non‐innocent role in activating the catalytic process. Additionally, it has been observed that for the same chiral descriptor (Δ‐at‐Ir or Λ‐at‐Ir), the major enantiomer formed depends on the nature of the cyclometalating ligand. These enantiodivergent results contravene the general assumption that the chiral‐at‐metal core's chirality dictates the sense of the chiral induction. A combined analysis of the main structural features of the catalysts deduced from XRD structures and in situ NMR spectroscopy allowed us to propose a simplified catalytic cycle and a working hypothesis to explain the observed enantioselectivities. [ABSTRACT FROM AUTHOR]

A Pd‐catalyzed asymmetric isomerization‐hydroamidocarbonylation of amide‐containing alkenes was developed, affording a variety of chiral α‐alkyl succinimides in moderate to good yields with high enantioselectivities. The key to success was introducing bulky 1‐adamentyl P‐substitution and 2,3,5,6‐tetramethoxyphenyl group into the rigid P‐chirogenic bisphosphine ligand to create stronger steric hinderance and deeper catalytic pocket. By this approach, regio‐ or stereo‐convergent synthesis of enantiomeric succinimides from the mixture of olefin isomers was achieved. [ABSTRACT FROM AUTHOR]

As a significant variant of the Michael reaction, the 1,6‐addition reaction has undergone considerable development over the past decade. This effective strategy enables the synthesis of a variety of novel and potentially bioactive functional molecules. In this review, we summarize the recent progress in NHC‐catalyzed 1,6‐addition reactions, highlighting their efficiency in the rapid synthesis of complex functional molecules. We also provide our perspectives on the future development of this dynamic and highly active research area. [ABSTRACT FROM AUTHOR]

An organocatalytic enantioselective [3+2] cycloaddition reaction involving 2-arylidene-1,3-indandiones and N-2,2-difluoroethylbenzothiophenone imines was developed. This approach efficiently afforded dispiro[benzothiophenone-indandione-pyrrolidine]s, featuring three stereocenters, in 84–98% yields with 3–93% ee and 9:1–>20:1 dr. Notably, the method maintained its yield and enantioselectivity integrity even in a gram-scale amplification experiment. For example, the product with substituents on aromatics were obtained in 90% yield with 91% ee and >20:1 dr. Its absolute configuration was established through X-ray single-crystal diffraction analysis, and a plausible reaction mechanism was proposed. [ABSTRACT FROM AUTHOR]

Planar‐chiral skeletons widely exist in natural products, bioactive compounds, and other functional molecules. Although significant progress has been made in the field of asymmetric synthesis of centrally or axially chiral molecules over the past years, enantioselective constructing of planar chirality is still a big obstacle and numerous efforts have been made in this field. Previous works have mainly focused on the assembly of planar‐chiral [2,2]‐paracyclophanes and metallocenes. This Minireview describes recent advancements in asymmetric catalytic synthesis of planar‐chiral macrocycles, including ansa chain construction, plane formation and asymmetric transformation strategies. It is anticipated that this Minireview will sever as a source of inspiration for developing new unconventional procedures for access to planar‐chiral skeletons. [ABSTRACT FROM AUTHOR]

Catalytic enantioselective preparation of alkene atropisomers with multiple stereogenic elements and discovery of their applications have become significant but challenging issues in the scientific community due to the unique structures of this class of atropisomers. We herein report the first catalytic atroposelective preparation of cyclopentenyl[b]indoles, a new kind of alkene atropisomers, with stereogenic point and axial chirality via an unusual rearrangement reaction of 3‐indolylmethanols under asymmetric organocatalysis. Notably, this novel type of alkene atropisomers have promising applications in developing chiral ligands or organocatalysts, discovering antitumor drug candidates and fluorescence imaging materials. Moreover, the theoretical calculations have elucidated the possible reaction mechanism and the non‐covalent interactions to control the enantioselectivity. This approach offers a new synthetic strategy for alkene atropisomers with multiple stereogenic elements, and represents the first catalytic enantioselective rearrangement reaction of 3‐indolylmethanols, which will advance the chemistry of atropisomers and chiral indole chemistry. [ABSTRACT FROM AUTHOR]

The organocatalytic asymmetric benzylation of Morita–Baylis–Hillman (MBH) carbonates with 2,4-dinitrotoluene derivatives as nucleophiles is described. The developed reaction provides a straightforward access to functionalized 2,4-dinitrotoluene derivatives of biological and synthetic relevance. Highly functionalized products have been chemoselectively and efficiently obtained in good to high yields (up to 84%) and with excellent stereoselectivity (up to >20:1 dr, >99 ee). [ABSTRACT FROM AUTHOR]

A new strategy for the asymmetric allylic alkylation of azlactones with α-(trifluoromethyl)allyl acetates catalyzed by Pd(OAc)2 /(R)-BINAP is designed and developed, providing access to unsaturated α-quaternary α-amino acid derivatives bearing a trifluoromethyl group and contiguous quaternary and tertiary stereogenic centers. The products are obtained in good yields with exclusive regioselectivity and excellent stereoselective control under relatively mild reaction conditions. A scale-up experiment shows no loss of reactivity or stereoselectivity. The synthetic utility of the current strategy is demonstrated through transformations of a representative product to afford several potentially bioactive species. [ABSTRACT FROM AUTHOR]

Despite the existence of three competing reactions for propargyloxyoxindoles, we report a chemoselectivity switch between enantioselective propargyl [2,3]‐Wittig rearrangement and Conia‐ene‐type reactions, with suppression of the [1,2]‐Wittig‐type rearrangement. Using C1‐symmetric imidazolidine‐pyrroloimidazolone pyridine as the ligand and Ni(acac)2 as the Lewis acid, diverse 3‐hydroxy 3‐substituted oxindoles containing allenyl groups were obtained in up to 98 % yield and 99 % ee via asymmetric propargyl [2,3]‐Wittig rearrangement. In the presence of AgOTf‐Duanphos, chiral spiro dihydrofuran oxindoles were given in up to 98 % yield and 91 % ee through a Conia‐ene‐type reaction. [ABSTRACT FROM AUTHOR]

An efficient and practical method was developed for the synthesis of C2‐symmetric 2,2′‐bipyridine‐α,α′‐1‐t‐butyl‐diol ligands. The disclosed synthesis involves the Ullmann homocoupling of a keto bromo‐pyridine under NiCl2/Zn/PPh3 conditions, followed by the stereoselective double hydrogen transfer to the obtained 2,2′‐bipyridine‐diketone using RuII Noyori–Ikariya catalysts. This approach allowed the successful synthesis of 2,2′‐bipyridine‐α,α′‐1‐t‐butyl‐diol, i.e (S,S)‐Bolm's ligand, with a quantitative yield and an excellent stereoselectivity (ee>99.5 %, de>99.5 %), with an overall yield of 69 % from easily accessible starting materials. [ABSTRACT FROM AUTHOR]

Since its discovery in the early 1950s, the sandwich‐type structure of ferrocene has sparked significant research into its applications across various disciplines, including asymmetric synthesis, medicinal chemistry, and materials science. Planar chiral ferrocenes play a crucial role in asymmetric catalysis by serving as essential scaffolds for chiral ligands and catalysts. Classical methods for synthesizing planar chiral ferrocenes often encounter limitations such as low atom economy and lengthy synthesis steps. In contrast, catalytic desymmetrization synthesis strategies offer a promising alternative due to their ability to enhance step and atom efficiency. This review highlights recent advancements in this field, particularly focusing on transition‐metal‐catalyzed C−H functionalization and catalytic enantioselective desymmetrization reactions. [ABSTRACT FROM AUTHOR]

Atropisomeric compounds have been discovered in pharmaceuticals and materials science, and their enantioselective syntheses have gained tremendous attention. Among strategies for catalytic atroposelective synthesis, desymmetrization provides robust and straightforward approaches to axially chiral biaryls. Due to the relative ease of substrate design compared to other atroposelective strategies, desymmetrization has emerged as a pivotal stage for converting fascinating chemistry into its atroposelective counterpart, despite challenges such as the formation of achiral products by subsequent catalytic reactions and the long distance between the reaction site and the stereogenic axis. This review offers a comprehensive overview of recent advancements in atroposelective desymmetrization using chiral organo‐ and metal catalysts, addressing challenges and solutions, and aims to provide insights into future developments in this field. [ABSTRACT FROM AUTHOR]

Tertiary phosphines have been recognized as powerful organocatalysts for the Michael reaction, which is one of the most important atom-economical methods for carbon-carbon and carbon-heteroatom bond construction. In the presence of tertiary phosphines, a vast array of Michael acceptors and Michael donors can be coupled with each other under neutral and metal-free conditions to produce useful densely functionalized molecules. This review highlights the role of phosphine-catalyzed Michael reaction in cutting-edge areas, such as asymmetric synthesis, natural products synthesis, drug design, and polymer material science. As the central part of catalysis science, the kinetic and mechanistic issues are also discussed when possible. The review is organized by the type of the Michael acceptor and the Michael donor used in the reaction. [ABSTRACT FROM AUTHOR]

Chiral pincer complexes, characterized by their rigid tridentate coordination framework, have emerged as powerful catalysts in asymmetric synthesis. This review provides a comprehensive overview of recent advancements in the development of chiral pincer-type ligands and their corresponding transition metal complexes. We highlight the latest progress in their application across a range of catalytic asymmetric reactions, including the (transfer) hydrogenation of polar and non-polar bonds, hydrophosphination, alkynylation, Friedel-Crafts reactions, enantioselective reductive cyclization of alkynyl-tethered cyclohexadienones, enantioselective hydrosilylation, as well as Aza–Morita–Baylis–Hillman reactions. The structural rigidity and tunability of chiral pincer complexes enable precise control over stereoselectivity, resulting in high enantioselectivity and efficiency in complex molecular transformations. As the field advances, innovations in ligand design and the exploration of new metal centers are expected to expand the scope and utility of these catalysts, bearing significant implications for the synthesis of enantioenriched compounds in pharmaceuticals, materials science, and beyond. [ABSTRACT FROM AUTHOR]

The synthesis of asymmetric organic molecules has experienced a huge development over the last few decades. Phase‐transfer catalysis has been proven to be one of the most powerful methods for these asymmetric transformations. However, the study of the mechanism of these catalysts and the different interactions that they can establish with the reactants has failed to keep pace. In the present study, the conjugate cyanation of two different α,β‐unsaturated ketones are studied in the presence of a well‐known alkaloid quinine‐derived PTC, along with different modifications. The study includes the comparison of different binding modes between the catalysts and the different reactants, the mechanistic study of the reaction and the analysis of the non‐covalent interactions established within the complexes and their role in the global enantioselectivity of the process. [ABSTRACT FROM AUTHOR]

In this study, we unveil a novel method for the asymmetric dearomatization of indoles under cobalt/photoredox catalysis. By strategically activating C−H bonds of amides and subsequent migratory insertion of π‐bonds present in indole as reactive partner, we achieve syn‐selective tetrahydro‐5H‐indolo[2,3‐c]isoquinolin‐5‐one derivatives with excellent yields and enantiomeric excesses of up to >99 %. The developed method operates without a metal oxidant, relying solely on oxygen as the oxidant and employing an organic dye as a photocatalyst under irradiation. Control experiments and stoichiometric studies elucidate the reversible nature of the enantiodetermining C−H activation step, albeit not being rate‐determining. This study not only expands the horizon of cobalt‐catalyzed asymmetric C−H bond functionalization, but also showcases the potential synergy between cobalt and photoredox catalysis in enabling asymmetric synthesis of complex molecules. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Phthalides serve as core structures pervasive in a wide array of natural products and drug molecules, which display a diverse array of biological activities. We report herein a highly efficient dynamic kinetic resolution of 3‐hydroxyphthalides by chiral isothioureas (ITUs) catalyzed asymmetric acylation, facilitating the effective synthesis of a variety of chiral phthalidyl esters with good yields and enantioselectivities. Notably, this reaction features mild reaction conditions, expansive substrate scope as well as good functional group compatibility. In addition, the practicality of this method is underscored by the large‐scale synthesis, reduced catalyst loading experiment and the synthesis of the chiral phthalidyl ester prodrug. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: The implementation of divergent protein engineering on the natural transaminase Vf‐ω‐TA led to the development of two effective mutants (M2 and M8), enabling the enzymatic synthesis of chiral amine precursors of Rivastigmine and Apremilast, respectively. The evolution of the enzymes was guided by crystal structures and a focused mutagenesis strategy, allowing them to effectively address the challenging ketone substrates with significant steric hindrance. Under the optimized reaction parameters, transamination proceeded smoothly in good conversions and with perfect stereochemical control (> 99% ee). These processes utilize inexpensive α‐methylbenzylamine as an amine donor and avoid the continuous acetone removal and costly LDH/GDH/NADH systems. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: The 21st century has witnessed a continuous evolution in the development of boron‐stereogenic chemistry. Since the 1990s, various innovations for the synthesis of tetracoordinate boron‐stereogenic compounds, which exhibited great potential applications, have been demonstrated by synthetic chemists. This paper reviews the significant progress and recent advances towards the assembly of enantioenriched boron‐stereogenic compounds, and hopes to shed light on new perspectives and inspire further research in this emerging field. [ABSTRACT FROM AUTHOR]

The Michael addition reaction, a cornerstone of contemporary organic synthesis, has witnessed a resurgence of interest owing to its ability to forge intricate carbon‐carbon and carbon‐heteroatom bonds. In the past few years, heterocyclic compounds have been rigorously used as Michael donors, owing to their architectural diversity and distinct reactivity with or without the presence of base/transition metals/organocatalysts. This review encapsulates the latest breakthroughs in chemistry involving Michael addition reaction using heterocyclic compounds as Michael donors. It delivers a comprehensive update on developments in Michael addition reaction triggered by potent heterocycles since 2017, highlighting novel and innovative methodologies, with strategic insights. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: The implementation of divergent protein engineering on the natural transaminase Vf‐ω‐TA led to the development of two effective mutants (M2 and M8), enabling the enzymatic synthesis of chiral amine precursors of Rivastigmine and Apremilast, respectively. The evolution of the enzymes was guided by crystal structures and a focused mutagenesis strategy, allowing them to effectively address the challenging ketone substrates with significant steric hindrance. Under the optimized reaction parameters, transamination proceeded smoothly in good conversions and with perfect stereochemical control (> 99% ee). These processes utilize inexpensive α‐methylbenzylamine as an amine donor and avoid the continuous acetone removal and costly LDH/GDH/NADH systems. [ABSTRACT FROM AUTHOR]

Comprehensive Summary Key Scientists Organoborons are commonly used building blocks for rapidly increasing molecular complexity. Although significant progress has been made in the selective functionalization of mono‐organoborons, the site‐selective functionalization of poly(organoborons) has attracted substantial interest in organic synthesis, pharmaceuticals, and agrochemicals due to the presence of multiple potential reaction sites. This review discusses various activation modes of the target C–B bond, with diverse transformations being achieved in both a selective and efficient manner. Recent advances in the catalytic selective transformations of 1,n‐diboronates through ionic and radical pathways are highlighted. Furthermore, we summarize the existing challenges and future research directions in this field.In 1993, Suzuki, Miyaura and coworkers developed a pioneering example of selective arylation towards cis‐1,2‐bis(boryl) alkenes, marking the inception of this field. The Morken group has made significant contributions to the asymmetric diboration of alkenes and realized elegant catalytic functionalization of these compounds since 2004. In 2016, Fernández and colleagues achieved the selective arylation of the internal C–B bond of tri(boronates). Since 2019, the Aggarwal group has developed efficient Giese‐type addition and selective arylation at the more substituted C–B bond of 1,2‐bis(boronic) esters through photoredox catalysis. The controllable regiodivergent alkynylation of 1,3‐bis(boronic) esters was developed by Gao and coworkers in 2023. Recently, Qin conducted elegant research on the programmable late‐stage functionalization of bridge‐substituted bicyclo[1.1.1]pentane (BCP) bis‐boronates. Since 2013, catalytic stereoselective transformations have been developed by several groups, including those led by Morken and Chen. This review summarizes the latest and most significant developments in this field since 1993. [ABSTRACT FROM AUTHOR]

Due to their molecular topology, atropisomers serve as highly valuable chiral frameworks for diverse applications across academic research and industry. Despite the availability of numerous established catalytic methods for their synthesis, there is still a high demand for the development of novel and resourceful strategies. In this concept article, we will detail our studies on the use of transient Lewis acid‐base interactions (LABI) as a dynamization strategy for the synthesis of (hetero)biaryl atropisomers by Dynamic Kinetic Resolution (DKR). The formation of cyclic transition states, resulting from the interaction between an acidic functionality and a basic counterpart, plays a key role in facilitating racemization by substantially reducing the barrier to atropisomerization. In this scenario, we have employed transformations aimed at neutralizing the acidic nature of the Lewis acid, ultimately leading to the formation of configurationally stable enantioenriched compounds. The design of substrates and the employment of stereoselective strategies based on transition metal and biocatalysis for their resolution is detailed. Specific emphasis on the preparation of axially chiral motifs commonly found in catalysis or medicinal chemistry will also be given. [ABSTRACT FROM AUTHOR]

Axially chiral diaryl ethers represent a distinct class of atropisomers, characterized by a unique dual C─O axes system, which have been found in a variety of natural products, pharmaceuticals, and ligands. However, the catalytic enantioselective synthesis of these atropoisomers poses significant challenges, due to the difficulty in controlling both chiral C─O axes, and their more flexible conformations. Herein, an efficient protocol for catalytic enantioselective synthesis of axially chiral diaryl ethers is presented using organocatalyzed asymmetric Povarov reaction‐enabled desymmetrization, followed by aromatizations. This method yields a wide range of novel quinoline‐based diaryl ether atropoisomers in good yields and high enantioselectivities. Notably, various aromatization protocols are developed, resulting in a diverse set of polysubstituted quinoline‐containing diaryl ether atropisomers. Thermal racemization studies suggested excellent configurational stabilities for these novel diaryl ether atropisomers (with racemization barriers up to 38.1 kcal mol−1). Moreover, this research demonstrates for the first time that diaryl ether atropisomers lacking the bulky t‐Bu group can still maintain a stable configuration, challenging the prior knowledge in the field. The fruitful derivatizations of the functional group‐rich chiral products further underscore the value of this method. [ABSTRACT FROM AUTHOR]

We have developed the Rh‐catalyzed enantioselective [2+2+2] cycloaddition of homopropargyl enamides (tosylamide‐tethered 1,6‐enynes) with alkynes to construct tetrahydroindole skeletons found in natural alkaloids and pharmaceuticals. This cycloaddition proceeds at room temperature in high yields and regio‐ and enantioselectivity with a broad substrate scope. The preparative scale reaction followed by substituent conversion on the nitrogen atom and the diastereoselective [4+2] cycloaddition with singlet O2 affords hexahydroindole‐diols bearing three stereogenic centers and variable substituents on the nitrogen. Mechanistic studies have revealed that the substituents of the enynes change the ratio of intramolecular and intermolecular rhodacycle formation when using terminal alkynes, varying the ee values of the cycloadducts. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: An efficient and highly stereoselective synthetic method to access polycyclic chromanes has been achieved through organocatalyzed one‐pot step‐wise reactions involving 2‐hydroxycinnamaldehydes, 2‐aminochalcones, and malononitrile as substrates. The reactions underwent a quintuple process by aza‐Michael/Michael/Knoevenagel/oxa‐Michael/aldol‐type reaction in sequence to give products bearing 3 new generated rings and 5 chiral centers in moderate to quantitative yields with excellent stereoselectivities. A novel retro‐reaction mechanism was discovered in the synthetic transformations of products. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Transition‐metal‐catalyzed asymmetric alkylation of aldehydes represents a straightforward strategy for the synthesis of chiral secondary alcohols. However, efficient methods using organoborons as coupling reagents are rare. Herein, we report a highly enantioselective nickel‐catalyzed alkylation reaction of aldehydes, using readily available alkylborons as nucleophiles. A wide variety of chiral secondary alcohols were prepared from commercially available aldehydes with high yields. The key to the excellent enantioselectivity and chemoselectivity was the employment of a bulky C2‐symmetric chiral NHC ligand. This protocol features excellent enantiocontrol, mild conditions, and good functional group compatibility. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Transition‐metal‐catalyzed asymmetric alkylation of aldehydes represents a straightforward strategy for the synthesis of chiral secondary alcohols. However, efficient methods using organoborons as coupling reagents are rare. Herein, we report a highly enantioselective nickel‐catalyzed alkylation reaction of aldehydes, using readily available alkylborons as nucleophiles. A wide variety of chiral secondary alcohols were prepared from commercially available aldehydes with high yields. The key to the excellent enantioselectivity and chemoselectivity was the employment of a bulky C2‐symmetric chiral NHC ligand. This protocol features excellent enantiocontrol, mild conditions, and good functional group compatibility. [ABSTRACT FROM AUTHOR]

The dehydro‐Diels–Alder (DDA) reaction is a powerful method for the construction of aromatic compounds. However, the enantioselective DDA reaction has been rarely developed, probably due to the competitive thermal reaction. Herein, we report a copper‐catalyzed enantioselective DDA reaction through vinyl cation pathway. The reaction leads to the atom‐economical synthesis of axially chiral phenyl and indolyl carbazoles in generally excellent yields with good to excellent atroposelectivities. This methodology represents the first example of non‐noble metal‐catalyzed enantioselective DDA reaction. Notably, new chiral ligand and organocatalyst derived from the constructed axially chiral carbazole are demonstrated to be useful in asymmetric catalysis. [ABSTRACT FROM AUTHOR]

A Pd‐catalyzed enantioselective aminosilylation of alkenes via tandem Aza‐Heck/silylation reaction under Pd/Sadphos catalysis is disclosed. A wide array of oxime esters and silicon reagents are tolerated, furnishing the chiral pyrrolines bearing one quaternary or two contiguous stereocenters in good yield with high enantioselectivity. Not only terminal alkenes but also tri‐substituented internal alkenes successfully participate in the reaction, delivering vicinal stereocenters in complete diastereoselectivity and high enantioselectivity. DFT study is conducted to probe the reaction pathway and the origin of the enantioselectivity, which revealed that the stereoinduction arises from the weak interaction between the aromatic ring of the substrate fragment and naphthyl group in the ligand. [ABSTRACT FROM AUTHOR]

Amino acids have a crucial role in the field of asymmetric organocatalysis for the production of chiral compounds with high added value and specific biological activity. In particular, proline offers high activity and stereoselectivity for catalyzing aldol reactions in organic solvents. However, proline‐based catalysts often lack water‐solubility, accessibility, catalytic performance, or recovery in aqueous media. This work reports the design of proline‐functionalized poly(methyl methacrylate) (PMMA) nanoparticles with a magnetic core that offer high availability of chiral units in water and high recyclability. A proline‐based copolymerizable surfactant is designed and integrated onto the surface of PMMA nanoparticles through a miniemulsion polymerization process without using additional surfactants. The miniemulsion technique allows the incorporation of magnetite to the system to create a magnetically separable catalyst. The chiral nanocatalyst presents a high diastereoselective catalytic activity for the intermolecular aldol reaction between p‐nitrobenzaldehyde and cyclohexanone in water. [ABSTRACT FROM AUTHOR]

Over the past decades, visible light‐mediated photocatalysis has found a mainstream of applications in synthetic chemistry. Organosilanes have been proven to be a useful class of electron donors to generate the highly active radical species via photoinduced single electron transfer oxidation/fragmentation sequence, which may undergo follow‐up radical coupling or addition process. This minireview highlights the comprehensive advances of organosilanes in photoredox catalyzed asymmetric organic synthesis, with particular emphasis placed on reaction mechanisms. We hope that this review will inspire further design and development of new reactions with such class of readily accessible reagents. [ABSTRACT FROM AUTHOR]

The catalytic application of chiral phosphoric acids (CPAs) from 2004 to date represents a true milestone for asymmetric organocatalysis. However, not only the free acids can be conveniently employed in numerous different asymmetric synthetic methodologies, thus being strictly compliant to the concept of "organocatalysis", but also their metal salts. This review focuses on asymmetric reactions in which the catalyst is a chiral alkali or alkaline‐earth metal phosphate. [ABSTRACT FROM AUTHOR]

A ruthenium‐catalyzed reductive amination via asymmetric transfer hydrogenation (ATH) has been used to perform an efficient dynamic kinetic resolution (DKR) of N‐aryl 2‐formyl pyrroles decorated with a phosphine moiety positioned at the ortho' position. The strategy relies on the labilization of the stereogenic axis in the substrate facilitated by a transient Lewis acid‐base interaction (LABI) between the carbonyl carbon and the phosphorus center. The reaction features broad substrate scope of aliphatic amines and N‐aryl pyrrole scaffolds, and proceeds under very mild conditions to afford P,N atropisomers in good to high yields and excellent enantioselectivities (up to 99 % ee) for both diphenyl and dicyclohexylphosphino derivatives. [ABSTRACT FROM AUTHOR]

Organic‐chemical literature encompasses large numbers of catalysts and reactions they can effect. Many of these examples are published merely to document the catalysts' scope but do not necessarily guarantee that a given catalyst is "optimal"—in terms of yield or enantiomeric excess—for a particular reaction. This paper describes a Machine Learning model that aims to improve such catalyst‐reaction assignments based on the carefully curated literature data. As we show here for the case of asymmetric magnesium catalysis, this model achieves relatively high accuracy and offers out of‐the‐box predictions successfully validated by experiment, e.g. in synthetically demanding asymmetric reductions or Michael additions. [ABSTRACT FROM AUTHOR]

Planar chirality, as one of the most important manifestations of chirality, is frequently employed to constrain three‐dimensional chiral configurations. Recent advancements in the study of planar chirality by chemists have opened up innovative possibilities for designing new catalysts, developing novel drugs, and creating new optical materials. However, the flexible ansa chains present a challenge during the synthesis process of these unique planar‐chiral macrocycles, hindering chemists from achieving high enantioselectivity. In this mini review, we primarily introduce the catalytic asymmetric synthesis methods that have been reported for late‐stage functionalization of planar macrocycles to generate planar chirality. Additionally, we present several recent examples of catalytic enantioselective synthesis of mechanically planar‐chiral rotaxanes through late‐stage functionalization methods. The sources of stereoselectivity are also discussed in this mini review. We aim to inform more researchers about this field and attract chemists to engage in this important and scientifically significant area of research. [ABSTRACT FROM AUTHOR]

Bis(alkenyl)boronates react with optically active Ir(π‐allyl) species in a process that involves allylation of the more substituted olefin and 1,2‐metalate shift of the less substituted olefin. The method constructs valuable enantioenriched tertiary allylic boronic esters with high chemoselectivity, enantioselectivity and diastereoselectivity. Allylic functionalization reactions transform the 1,3‐stereodiad to 1,5‐ and 1,6‐stereochemical relationships. [ABSTRACT FROM AUTHOR]

Functionalization of Si‐bound methyl group provides an efficient access to diverse organosilanes. However, the asymmetric construction of silicon‐stereogenic architectures by functionalization of Si‐bound methyl group has not yet been described despite recent significant progress in producing chiral silicon. Herein, we disclosed the enantioselective silylmethyl functionalization involving the aryl to alkyl 1,5‐palladium migration to access diverse naphthalenes possessing an enantioenriched stereogenic silicon center, which are inaccessible before. It is worthy to note that the realization of asymmetric induction at the step of metal migration itself remains challenging. Our study constitutes the first enantioselective aryl to alkyl 1,5‐palladium migration reaction. The key to the success is the discovery and fine‐tuning of the different substituents of α,α,α,α‐tetraaryl‐1,3‐dioxolane‐4,5‐dimethanol (TADDOL)‐based phosphoramidites, which ensure the enantioselectivity and desired reactivity. [ABSTRACT FROM AUTHOR]

The introduction of allyl fluorides as alternative electrophiles in asymmetric allylic alkylation reactions has recently attracted significant interest. Despite the intrinsic thermodynamically demanding C–F bond-cleavage event, the fluorophilic nature of the silicon atom is key in assisting the activation and cleavage of the allylic C–F bond. Thus, the use of silylated compounds as unconventional nucleophiles, together with the Lewis basicity of fluorine when acting as a leaving group, enables the development of innovative chemical transformations within mild and selective catalytic schemes. This Synpacts article summarizes the diverse defluorinative asymmetric allylic alkylations with allyl fluorides reported to date under both chiral Lewis base and transition-metal catalysis. [ABSTRACT FROM AUTHOR]