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Comprehensive Summary: Transition metal‐catalyzed difunctionalization of tethered alkene has emerged as a prevailing tool for the expedient construction of synthetically valuable cyclic compounds. However, most efforts have been devoted to the reaction of styrene‐type substrates due to their rigid scaffold and high reactivity. With respect to the difunctionalization of nonaromatic tethered olefin, especially the mono‐substituted alkene, still remains largely underdeveloped. Herein, we disclose a nickel/Quinim complex and TBADT‐cocatalyzed asymmetric carbamoyl‐acylation of unactivated alkene tethered on nonaromatic carbamoyl chlorides with diverse aldehydes. The reaction exhibits broad substrate scope with good functional group tolerance, as well as high reaction efficiency and enantioselectivity. Both monosubstituted and 1,1‐substituted alkenes can work well with either aliphatic or aromatic aldehydes under the current protocol, providing convenient access to an array of medicinally useful chiral γ‐lactams derivatives bearing a convertible acyl functionality. This reaction showcases more application possibilities of the chiral Quinim ligand in the future asymmetric catalytic transformations. [ABSTRACT FROM AUTHOR]

d-pantolactone is an intermediate in the synthesis of d-pantothenic acid, which is known as vitamin B5. The commercial synthesis of d-pantolactone is carried out through the selective resolution of dl-pantolactone catalyzed by lactone hydrolase. In contrast to a kinetic resolution approach, the deracemization of dl-pantolactone is a simpler, greener, and more sustainable way to obtain d-pantolactone with high optical purity. Herein, an efficient three-enzyme cascade was developed for the deracemization of dl-pantolactone, using l-pantolactone dehydrogenase from Amycolatopsis methanolica (AmeLPLDH), conjugated polyketone reductase from Zygosaccharomyces parabailii (ZpaCPR), and glucose dehydrogenase from Bacillus subtilis (BsGDH). The AmeLPLDH was used to catalyze the dehydrogenated l-pantolactone into ketopantolactone; the ZpaCPR was used to further catalyze the ketopantolactone into d-pantolactone; and glucose dehydrogenase together with glucose fulfilled the function of coenzyme regeneration. All three enzymes were co-expressed in E. coli strain BL21(DE3), which served as the whole-cell biocatalyst. Under optimized conditions, 36 h deracemization of 1.25 M dl-pantolactone d-pantolactone led to an e.e.p value of 98.6%, corresponding to productivity of 107.7 g/(l·d). [ABSTRACT FROM AUTHOR]

Chiral cyclopropane derivatives are essential in synthetic chemistry and drug discovery. Their synthesis commonly relies on asymmetric cyclopropanation of diazo compounds, potentially explosive and needing stabilizing substituents. Thus, asymmetric catalytic transformations of non‐stabilized carbenes or carbenoids remain a formidable challenge. Herein, we report the unprecedented chromium‐catalyzed asymmetric cyclopropanation of readily available gem‐dihaloalkanes and terminal olefins. Distinct from previous approaches, gem‐dihaloalkanes serve as suitable precursors for non‐stabilized carbenes or carbenoids, furnishing various functionalized chiral cyclopropanes. Mechanistic studies, including radical trapping, non‐linear effect, and UV/Vis spectroscopy, provide insights into the catalytic process, featuring radical‐polar crossover. [ABSTRACT FROM AUTHOR]

The catalytic methodologies for the derivatization of aza‐QM have recently appeared in the literature and involve organocatalytic and organometallic approaches. This review aims at analyzing the diverse catalytic systems involving chiral NHC carbenes, phosphoric acids, phosphoramidites, phosphine and copper and palladium catalysis showing its applicability for the synthesis of a diverse away of N‐containing compounds which in many cases have biological activity. [ABSTRACT FROM AUTHOR]

Asymmetric organocatalysis is a robust methodology providing access to numerous valuable compounds while having green chemistry principles in mind. The realization of organocatalytic transformation under solvent‐free mechanochemical conditions brings additional benefits in terms of yields, selectivities, and, last but not least overall improved sustainability. This overview describes developments in the use of mechanochemistry as a vehicle for asymmetric organocatalytic transformations. The material is organized according to main catalytic activation modes, starting with covalent activation and proceeding to non‐covalent activation modes. The advantages of mechanochemical organocatalytic reactions are particularly highlighted, but in some cases also, limitations are mentioned. Possibilities for target compound synthesis are also discussed. [ABSTRACT FROM AUTHOR]

In this personal account, we describe our recent advances in the three types of phase‐transfer catalysis for various transformations including asymmetric induction: Firstly, asymmetric phase‐transfer catalysis with Maruoka‐type C2‐symmetric chiral biaryl‐modified tetraalkylammonium salts and phosphonium salts; Secondly, asymmetric phase‐transfer catalysis under base‐free and neutral conditions; Thirdly, hydrogen‐bonding catalysis using tetraalkylammonium and trialkylsulfonium salts. These three different strategies are illustrated by using various phase‐transfer catalyzed transformations. [ABSTRACT FROM AUTHOR]

Carbonyl transformations involving enolates and/or enamines have been used for various types of bond‐forming reactions. In this account, catalysts and catalyst systems that have amino acids or primary, secondary, and/or tertiary amines as key catalytic functional groups that we have developed to accelerate chemical transformations, including regio‐, diastereo‐ and enantioselective reactions, are discussed. Our chemical transformation strategies and methods that use amine derivatives as catalysts are also discussed. As amines can have different functions depending on protonation and on the species formed during the catalysis (such as enamines and iminium ions), dynamics and kinetic controls are the keys for understanding the catalysis. Further, strategies that harness dynamic steps and kinetic control in amine‐catalyzed reactions have enabled the synthesis of complex molecules in stereocontrolled manners. Understanding the dynamic features and the kinetic controls of the catalysis will further the design of the catalysts and the development of chemical transformation strategies and methods. [ABSTRACT FROM AUTHOR]

We report the first case of mechanochemical deracemization by using liquid‐assisted abrasive grinding. The target molecule is a precursor of Paclobutrazol, an important fungicide and plant growth inhibitor. Using mechanochemical deracemization, we are even able to transform a 10 % ee scalemic mixture of this latter in an enantioenriched product of 97 % ee in a couple of hours. This is substantially shorter compared to solution‐based deracemization methodologies. The present paper thus introduces an efficient and greener process to enantiopure material. [ABSTRACT FROM AUTHOR]

The investigation of chirality at the nanoscale is important to bridge the gap between molecular and macroscopic chirality. Atomically precise metal nanoclusters provide an ideal platform for this research, while their enantiopure preparation poses a challenge. Here, we describe an efficient approach to enantiopure metal nanoclusters via asymmetric transformation, that is, achiral Au23(SC6H11)16 nanoclusters are converted into chiral and enantiopure Au24(L)2(SC6H11)16 nanoclusters by a chiral inducer phosphoramidite (L). Two enantiomers of Au24(L)2(SC6H11)16 are obtained and the crystal structures reveal their hierarchical chirality, which originates from the two introduced chiral L molecules, the transformation-triggered asymmetric rearrangement of the staple motifs on the surface of the gold core, and the helical arrangement of nanocluster molecules. The construction of this type of enantiomerically pure nanoclusters is achieved based on the easy-to-synthesize and modular L. Lastly, the chirality-related chiroptical performance was investigated, revealing a negative nonlinear CD-ee dependence. Atomically precise metal nanoclusters provide an ideal platform for studying chirality at the nanoscale. Here, the authors use a phosphoramidite ligand as a chiral inducer to asymmetrically transform achiral into chiral gold nanoclusters with negative nonlinear CD-ee dependence. [ABSTRACT FROM AUTHOR]

The atom‐ and step‐efficient synthesis of chiral fused tricyclic lactams from readily available ketoesters using cheap ammonium salts as the nitrogen source is reported. This ruthenium‐catalyzed system operates through an efficient tandem dynamic kinetic asymmetric reductive amination (ARA)/lactamization and produces chiral fused tricyclic lactams in high yields with excellent diastereo‐ and enantioselectivity (up to >99 % ee, >20 : 1 dr and 98 % yield). The robust method was also applied to the concise synthesis of key intermediates in the synthesis of rivastigmine analogues and chiral N‐heterocyclic carbene catalysts. [ABSTRACT FROM AUTHOR]

A variety of biaryl polyketides exhibit remarkable bioactivities. However, their synthetic accessibility is often challenging. Herein, the enantioselective preparation and synthetic application of an axially chiral 2,2'‐biphenol building block is outlined that represents a common motif of these intriguing natural products. Based on the highly regioselective and scalable bromination of a phenol precursor, a coupling process by Lipshutz cuprate oxidation was developed. A copper‐mediated deracemization strategy proved to be superior to derivatization or kinetic resolution approaches. Key steps in the overall building block synthesis were rationalized through DFT studies. Utilizing the 2,2'‐biphenol, a highly diastereoselective five step synthesis of formerly unknown (+)‐di‐epi‐gonytolide A was developed, thus showcasing the building block's general potential for the synthesis of natural products and their derivatives. En route, the first enantioselective construction of a chromone dimer intermediate was established. [ABSTRACT FROM AUTHOR]

The synthesis of enantiopure chiral cyclic amines is of critical importance but highly challenging. In this study, a metal‐enzyme hybrid catalyst was fabricated by the co‐immobilization of palladium nanoparticles and monoamine oxidases on dendritic organosilica nanoparticles (DONs) for chemoenzymatic deracemization, furnishing a panel of chiral cyclic amines in high enantioselectivities (96–98 % ee). Catalyst optimization revealed that the ultra‐high specific surface area, mesoporous channels and hydrophobic microenvironment of the DONs are responsible for the improved catalyst stability, activity and catalytic efficiency. [ABSTRACT FROM AUTHOR]

[Display omitted] • This paper provides a complete and quick overview of nonenzymatic catalytic deracemization, which depends on two major strategies: the redox-driven deracemizaiton and the photochemical deracemization. • Reasonably regulating redox operation could enable a redox deracemization process thermodynamically feasible by destructing and regenerating the chirality of molecule with a linear or cyclic mode. • An effective visible-light-driven deracemization would be successfully promoted when using the proper photocatalysts upon illumination of light, because energy from light can compensate for the entropy decrease and thus provide a strong thermodynamic driving force for a deracmerization. Deracemization, a highly appealing method to synthesize the optically pure compounds, is defined as the conversion of a racemic mixture into a single enantiomer of the same compound in theoretically 100 % yield by increasing the quantity of one enantiomer at the expense of the other. This highlight article focuses on recent progress in catalytic deracemization under pure chemical reaction conditions, excluding biocatalysed deracemization procedures and spontaneous deracemization by crystallization. This survey is divided in two main sections:1) redox-driven deracemization enabled by sequential oxidation/reduction operation or a compatible redox system; 2) photochemical deracemization via selective energy transfer, hydrogen-atom and proton transfer. Especially, the latter has gained a big breakthrough that may open up new avenues for nonenzymatic catalytic deracemization. [ABSTRACT FROM AUTHOR]

To tackle the asymmetric input constraint typically involved with industrial temperature control systems, e.g., there is a tuning range from 0 to 100% in the heating power, an anti-windup active disturbance rejection control (ADRC) is proposed for the practical application, in particular for dealing with output delay. Based on an artificial symmetric transformation for the asymmetric input constraint along with a delay-free output prediction, an anti-windup extended state observer (AESO) is firstly constructed to simultaneously estimate the delay-free system state and external disturbance for control design. When the input saturation constraint occurs, the proposed AESO could also offer anti-windup compensation. Then, a feedback controller is analytically derived by assigning repetitive-type poles for the characteristic equation of the closed-loop structure, followed by a set-point prefilter design to ensure no overshoot and output tracking deviation. Tractable linear matrix inequality based conditions are rigorously established to guarantee the asymptotic stability of the resulting closed-loop system under a specified initial condition. A benchmark example from a recent reference is used to verify the superiority of the proposed control method over some existing anti-windup control designs. Moreover, a real application to the temperature control of a jacketed crystallizer is shown in comparison with a recently developed control method with no anti-windup compensation. • Novel anti-windup control design against asymmetric input saturation. • Active disturbance rejection control (ADRC) design for temperature control systems. • Anti-windup extended state observer for estimating the system state and disturbance. • Sufficient conditions are established for maintaining the system stability. • A real application to the temperature control of a jacketed crystallizer. [ABSTRACT FROM AUTHOR]

Biocatalytic processes are increasingly used in organic synthesis for the preparation of targeted molecules or the generation of molecular diversity. The search for the biocatalyst is often the bottleneck in the development of the process. We described a combinatorial approach for the selection of active strains from a library of microorganisms. In order to show the potential of the method we applied it to a mixture of substrates. We were able to select yeast strains capable of producing enantiopure alcohol from corresponding ketones with very few tests and highlight tandem reaction sequences involving several microorganisms. We demonstrate an interest in the kinetic study and the importance of incubation conditions. This approach is a promising tool for generating new products. [ABSTRACT FROM AUTHOR]

Asymmetric catalysis has long been recognized as a powerful tool for the synthesis of enantioenriched molecules. In addition to precise enantiocontrol, high-atom economy, which is crucial for practicality, has always been pursued by chemists in the development of methodologies. Consequently, deracemization, the direct conversion of a racemic compound to one of its enantiomers, and thus characterized by a 100% atom efficiency, has attracted increasing interest. Recently, visible-light-driven photocatalysis has been demonstrated to be a promising platform for the development of deracemization. Central to its success is its ability to efficiently overcome the prevailing kinetic issues in chemical transformations and the intrinsic thermodynamic challenges, which typically require the use of additional stoichiometric reagents, thus undermining the original advantages. In this review, the advances in this attractive area are systematically summarized and discussed, with examples organized according to the different modalities of energy transfer and single-electron transfer in photocatalysis. [ABSTRACT FROM AUTHOR]

Based upon their exceptional reactivity as cooperative Brønsted acid‐base catalysts chiral diphosphane Pd‐aqua complexes have successfully been utilized in a broad range of asymmetric transformations. Originally discovered by Sodeoka 25 years ago, they readily form reactive chiral Pd enolates upon deprotonation of β‐dicarbonyl compounds and simultaneously, a Brønsted acid liberated from the catalyst activates the electrophile. After the initial report and some ensuing papers had been published in the early 2000s, the field lay dormant for more than a decade. In recent years, however, new developments towards the enantioselective synthesis of various heterocycles and other useful compounds have evolved which take advantage of the unique properties of chiral Pd‐aqua complexes. [ABSTRACT FROM AUTHOR]

The present work describes an unprecedented blueprint for the chiral (S)-1,1′-Bi-2-naphthol ligand (BINOL) immobilized on amine functionalized mesoporous silica nanoparticles (MSNs) via a linker, which is then converted into a ruthenium complex, i.e., Ru-BINOL-AP@MSNs (where AP = (3-aminopropyl)trimethoxysilane), without the use of deprotecting or protecting groups. Using a variety of techniques, such as FTIR, N2 adsorption–desorption isotherms, solid-state 13C CP MAS NMR, powder XRD, FESEM, HRTEM, XPS, and thermogravimetric analysis, the as-synthesized catalyst was persuasively verified. Asymmetric transformations of enantiomerically enriched chiral alcohols can be achieved with the aforesaid active catalytic precursors, making the proposed method even more appealing. During the asymmetric hydrogenation reaction, the Ru-BINOL-AP@MSNs catalyst proved to be catalytically competent, leading to an 84% conversion with an enantioselectivity >90% of the R-isomer. Furthermore, the synthesized catalyst was capable of being recycled five consecutive times with only a minute loss of its effectiveness, thereby reducing solvent waste and precious metal or ligand losses. [ABSTRACT FROM AUTHOR]

Deracemization extended to racemic‐compound‐forming systems is demonstrated. We present here the first results of an alternative for the resolution of systems that exhibit a stable racemic compound but also a closely related conglomerate‐forming system. If the couples of enantiomers forming the racemic compound and the enantiomers of the stable conglomerate can syncrystallize in mirror‐related partial solid solutions, it is possible to deracemize the racemic mixture of mixed crystals to access to a single handedness. The evidence for this possibility is given in three examples by using temperature‐cycling‐induced deracemization. [ABSTRACT FROM AUTHOR]

The first organocatalytic, non‐destructive desymmetrisation of 3‐substituted cyclobutanone followed by intramolecular cyclisation is described. Owing to the slow activation of the pronucleophile by the weak Brønsted base, the α‐functionalization of ketones with tertiary‐amine‐derived Brønsted base catalysis has been chemically challenging in asymmetric transformations. Herein, we demonstrate that the cinchona‐derived squaramide catalyst works effectively for the intramolecular Michael addition of cyclobutanone to enones and affords the architecturally fascinating [6,5,4]‐fused carbocyclic skeleton in good yields and excellent diastereo‐ and enantioselectivities (up to >20 : 1 dr and 96 % ee). Furthermore, as a synthetic application, this method provides an alternative pathway to enantioenriched high‐value products like γ‐lactones and indan‐2‐ol derivatives. [ABSTRACT FROM AUTHOR]

Chiral phosphoric acids (CPAs) and their salts are the privileged catalysts in a plethora of asymmetric transformations. All of the scaffolds of efficient CPAs rely on C2‐symmetry and axial chirality, while the only examples of punctually chiral CPAs are TADDOL derivatives. Herein, we present the design and the synthesis of C2‐symmetric cycloglycerophosphates (cGPAs) and their application throughout the addition of trimethylsilyl cyanide (TMSCN) to aldehydes and ketones, to obtain the corresponding cyanohydrins in yields between 77 and 99% and ee between 84.2 and 99.5% (27 examples). A DFT computational model is moreover performed to rationalize the reaction mechanism and its stereochemical outcome. [ABSTRACT FROM AUTHOR]

A catalytic asymmetric 1,3-dipolar cycloaddition between iminoesters derived from 5-hydroxymethylfurfural (HMF) and different activated alkenes is reported. Excellent levels of diastereo and enantioselectivity were obtained when Fesulphos/CuI complex was used as catalyst. This metodology provides an effective and sustainable access to challenging enantioenriched heterocyclic scaffolds and represents one of the rare examples of catalytic asymmetric transformations using HMF as a starting material. [ABSTRACT FROM AUTHOR]

d -(−)-Pantolactone (DPL) is a key intermediate for the production of d -(+)-pantothenate (vitamin B5). Deracemization of d , l -pantolactone (D, L -PL) through oxidizing l -(+)-pantolactone (LPL) to ketopantoyl lactone (KPL) and subsequently reducing KPL to DPL is a promising route for synthesizing DPL. Herein, a newly mined l -pantolactone dehydrogenase from Rhodococcus hoagie (Rho LPLDH) was used for the oxidative dehydrogenation of LPL. To alleviate inclusion bodies formed by membrane-bound Rho LPLDH intracellular expression in E. coli , strategies involving chaperone assistance and decreasing induction temperature were used to achieve Rho LPLDH soluble expression. To enhance its activity, directed evolution and hydrophilicity-based engineering yielded increased catalytic activity and thermostability. 1 M LPL was efficiently converted to KPL by engineering strain CM5 co-expressing Rho LPLDHL254I/V241I/I156L/F224Q/N164K and chaperone. A "two stages in one-pot" method was employed in deracemization of 1 M D, L -PL with 91.2% yield. These results demonstrated that CM5 catalyst exhibits great potential in enzyme cascade deracemization for the production of DPL. • First heterologous soluble expression of l -pantolactone dehydrogenase (LPLDH). • Hydrophilicity-based engineering enhanced the activity and thermostability of LPLDH. • Catalyst CM5 was applied in deracemization of 1 M D, L -PL obtaining 91.2% DPL yield. [ABSTRACT FROM AUTHOR]

Despite the great interest in carborane-containing molecules, there is a lack of literature on the generation of central chiralities, via catalytic asymmetric transformations using prochiral carboranyl substrates. Herein, we have synthesized novel optically active icosahedral carborane-containing diols via Sharpless catalytic asymmetric dihydroxylation of carborane-derived alkenes, under mild conditions. The reaction showed a good substrate scope with 74–94% yields and 92–>99% ee. This synthetic approach facilitated the creation of two adjacent stereocenters respectively located at the α,β-position of o-carborane cage carbon, with a single syn-diastereoisomer. In addition, the obtained chiral carborane-containing diol product can be transformed to cyclic sulfate and can subsequently undergo a nucleophilic substitution and reduction to obtain the unexpected nido-carboranyl derivatives of chiral amino alcohols in the form of zwitterions. [ABSTRACT FROM AUTHOR]

Free carbene readily causes multiple side reactions due to its high energy, thus its asymmetric transformation is very difficult. We present here our findings of high‐pKa Brønsted acid catalysts that enable free carbene insertion into N−H bonds of amines to prepare chiral α‐amino acid derivatives with high enantioselectivity. Under irradiation with visible light, diazo compounds produce high‐energy free carbenes that are captured by amines to form free ylide intermediates, and then the newly designed high‐pKa Brønsted acids, chiral spiro phosphamides, promote the proton transfer of ylides to afford the products. Computational and kinetic studies uncover the principle for the rational design of proton‐transfer catalysts and explain how the catalysts accelerate this transformation and provide stereocontrol. [ABSTRACT FROM AUTHOR]

We demonstrate that a conglomerate-forming clopidogrel precursor undergoing solution phase racemization can be deracemized through cyclic solvent removal and re-addition. We establish that the combination of slow growth and fast dissolution of crystals is ideal for rapid deracemization, which we achieve by repurposing a Soxhlet apparatus to realize the slow removal and fast re-addition of solvent autonomously. [ABSTRACT FROM AUTHOR]

Asymmetric Brønsted acid catalysis has been recognized as a powerful concept for asymmetric synthesis. In the process of pursuing more robust and highly effective chiral Brønsted acid catalysts, chiral bisphosphoric acids have received much attention in the last two decades. Their unique catalytic properties are mainly attributed to the inherent intramolecular hydrogen bonding interactions that could increase the overall acidity and tune the conformation property. Integrating hydrogen bonding into the catalyst design, quite a few structurally unique and effective bisphosphoric acids have been synthesized, which frequently exhibited superior selectivity in a broad range of asymmetric transformations. This review summarizes the status quo of chiral bisphosphoric acid catalysts and their applications in catalyzing asymmetric transformations. [ABSTRACT FROM AUTHOR]

In this work we review research activities on a few of the most relevant structural aspects of bilirubin (BR) and biliverdin (BV). Special attention is paid to the exocyclic C=C bonds being in mostly Z rather than E configurations, and to the overall conformation being essentially different for BR and BV due to the presence or absence of the double C=C bond at C-10. In both cases, racemic mixtures of each compound of either M or P configuration are present in achiral solutions; however, imbalance between the two configurations may be easily achieved. In particular, results based on chiroptical spectroscopies, both electronic and vibrational circular dichroism (ECD and VCD) methods, are presented for chirally derivatized BR and BV molecules. Finally, we review deracemization experiments monitored with ECD data from our lab for BR in the presence of serum albumin and anesthetic compounds. [ABSTRACT FROM AUTHOR]

Asymmetric catalytic transformations of N‐unprotected cyclic carboxyimides such as succinimides, hydantoins, oxazolidinediones, and glitazones, is a powerful way of directly accessing variety of biologically valuable chiral compounds. Herein, a bis(trichlorosilyl) nucleophilic intermediate formed from cyclic carboxyimides was reacted with aldehydes via (S)‐SEGPHOS dioxide (SEGPHOSO), proceeding the aldol reaction in highly enantioselective fashion through a cyclic transition state. Furthermore, N‐unprotected carboxyimides were chemoselectively activated, even in the presence of N‐alkylated carboxyimides, to undergo stereoselective and chemoselective aldol reactions via in situ silicon tetrachloride activation. The functionalized cyclic carboxyimides is readily derived to the several synthetic units derivatization to various chiral building blocks without unnecessary protection/deprotection steps. [ABSTRACT FROM AUTHOR]

Biocatalytic cascade conversion of racemic amines into optically pure ones using enantiocomplementary ω-transaminases (ω-TAs) has been developed by thermodynamic and kinetic control of reaction pathways where 12 competing reactions occur with pyruvate and isopropylamine used as cosubstrates. Thermodynamic control was achieved under reduced pressure for selective removal of a coproduct (i.e., acetone), leading to elimination of six undesirable reactions. Engineered orthogonality in substrate specificities of ω-TAs was exploited for kinetic control, enabling suppression of four additional reactions. Taken together, the net reaction pathway could be directed to two desired reactions (i.e., oxidative deamination of R-amine and reductive amination of the resulting ketone into antipode S-amine). This strategy afforded one-pot deracemization of various chiral amines with >99% eeS and 85-99% reaction yields of the resulting S-amine products. The in vitro cascade reaction could be successfully implemented in a live microbe using glucose or l-threonine as a cheap amino acceptor precursor, demonstrating a synthetic metabolic pathway enabling deracemization of chiral amines which has never been observed in living organisms.

d-Amino acids are pharmaceutically important building blocks, leading to a great deal of research efforts to develop cost-effective synthetic methods. Preparation of d-amino acids by deracemization has been conceptually attractive owing to facile synthesis of racemic amino acids by Strecker synthesis. Here, we demonstrated biocatalytic deracemization of aliphatic amino acids into d-enantiomers by running cascade reactions; (1) stereoinversion of l-amino acid to a d-form by amino acid dehydrogenase and ω-transaminase and (2) regeneration of NAD+ by NADH oxidase. Under the cascade reaction conditions containing 100 mM isopropylamine and 1 mM NAD+, complete deracemization of 100 mM dl-alanine was achieved after 24 h with 95% reaction yield of d-alanine (> 99% eeD, 52% isolation yield). Graphical Abstract: [Figure not available: see fulltext.].

The stereodivergent synthesis of allene compounds bearing α,β‐adjacent central chiralities has been realized via the Pd/Cu‐catalyzed dynamic kinetic asymmetric alkylation of racemic allenylic esters. The matched reactivity of bimetallic catalytic system enables the challenging reaction of racemic aryl‐substituted allenylic acetates with sterically crowded aldimine esters smoothly under mild reaction conditions. Various chiral non‐natural amino acids bearing a terminal allenyl group are easily synthesized in high yields and with excellent diastereo‐ and enantioselectivities (up to >20 : 1 dr, >99 % ee). Importantly, all four stereoisomers of the product can be readily accessed by switching the configurations of the two chiral metal catalysts. Furthermore, the easy interconversion between the uncommon η3‐butadienyl palladium intermediate featuring a weak C=C/Pd coordination bond and a stable Csp2−Pd bond is beneficial for the dynamic kinetic asymmetric transformation process (DyKAT). [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Alkynes are one of the most significant functional groups in organic chemistry and great efforts have been made to explore efficient approach for the construction of chiral alkynes. The asymmetric C(sp3)–C(sp) cross‐coupling provides a significant complementary strategy through radical‐initiated process. However, the stereocontrol of highly reactive and unstable radical intermediate has been a challenge for decades. To address this problem, a variety of chiral ligands are developed for initiating the reaction and achieving enantiocontrol of alkyl radicals. This review summarizes recent developments in copper‐catalyzed enantioselective alkynylation of prochiral alkyl radicals and their brief mechanistic studies. [ABSTRACT FROM AUTHOR]

This work aims to compare and explore the different catalytic efficiencies of structurally similar α- and β-amino acids in an asymmetric aldol transformation. Interestingly, aspartic acid is not only an α-amino acid, but also a β-amino acid. Thus, by modifying one of the two acidic groups of aspartic acid, two sets of α- and β-amino acids, 14 amino acids in total, were prepared and used as organocatalysts. The two types of amino acid, interestingly, achieved similar high catalytic efficiencies in the asymmetric aldol transformation under different optimal conditions. The ideal β-amino acid, in some cases, even achieved significantly higher enantioselectivity than the ideal α-amino acid, although α-amino acids are extensively demonstrated to be highly efficient organocatalysts in this asymmetric transformation. [ABSTRACT FROM AUTHOR]

2‐Aminoallyl cations are versatile 1,3‐dipoles that could potentially be used for diverse (3+n) cycloaddition reactions. Despite some preliminary studies, the asymmetric catalytic transformation of these species is still underdeveloped. We herein report a binuclear copper‐catalyzed generation of 2‐aminoallyl cations from ethynyl methylene cyclic carbamates and their enantioselective (3+2) cycloaddition reaction with indoles to construct chiral pyrroloindolines. This transformation features a novel C1,N‐dipolar reactivity for 2‐aminoallyl cations. [ABSTRACT FROM AUTHOR]

Diol scaffolds have been utilized as highly effective catalysts and ligands in a wide range of catalytic asymmetric transformations. For scaffolds to be successful as broadly used motifs, they should be prepared cheaply through facile routes and be easily handled. Herein, the synthesis of a family of planar chiral diols based on a modular and robust three‐step route is described, which yields catalytically active diols in >99 % de and >99 % ee, with up to seven different chiral elements. These diols have been characterized by X‐ray crystallographic analysis, which provides clear evidence for the likely transition state when applied in the asymmetric hetero‐Diels‐Alder reaction. Without altering the stereochemistry of the catalyst backbone, it is possible to access both enantiomers of the product by varying the substitution of the catalyst at the α‐position. [ABSTRACT FROM AUTHOR]

Diastereomeric salt crystallization is a convenient method to resolve chiral drug substances when other separation methods like preferential crystallization and solid-state deracemization cannot be applied directly. This is the case of the antiepileptic pregabalin, which is a racemate-forming compound with recently discovered hydrate-forming activity. In this study, the quaternary system of pregabalin enantiomers, L -tartaric acid and water was investigated by the characterization of relevant solid forms and the measurement of solubilities and solid–liquid equilibria. This information was used to outline phase diagrams in the specific quaternary space and create a thermodynamic model based on solubility product constants to simulate the effect of variable parameters on the resolution process. Thus, a set of optimal temperature pairs were identified with similar selectivity along the so-called purity line in the region of 10–40 °C. This line was adjusted experimentally, and a realistic correction of 3 °C was made. Our method provided a quick process with low material requirements to design diastereomeric salt resolution. Finally, a proof of concept resolution experiment was conducted, where a diastereomerically pure product was obtained with 51.6% yield and 153 mg (g water)−1 productivity. [ABSTRACT FROM AUTHOR]

Halohydrin dehalogenases are promiscuous biocatalysts, which enable asymmetric ring opening reactions of epoxides with various anionic nucleophiles. However, despite the increasing interest in such asymmetric transformations, the substrate scope of G‐type halohydrin dehalogenases toward cyclic epoxides has remained largely unexplored, even though this subfamily is the only one known to display activity with these sterically demanding substrates. Herein, we report on the exploration of the substrate scope of the two G‐type halohydrin dehalogenases HheG and HheG2 and a newly identified, more thermostable member of the family, HheG3, with a variety of sterically demanding cyclic epoxides and anionic nucleophiles. This work shows that, in addition to azide and cyanide, these enzymes facilitate ring‐opening reactions with cyanate, thiocyanate, formate, and nitrite, significantly expanding the known repertoire of accessible transformations. [ABSTRACT FROM AUTHOR]

Catalytic carbene transfer reactions are fundamental transformations in modern organic synthesis, which enable direct access to diverse structurally complex molecules. Despite diazo precursors playing a crucial role in catalytic carbene transfer reactions, most reported methodologies take into account only diazoacetates or related compounds. This is primarily because diazoalkanes, unless they contain a resonance stabilizing group, are more susceptible to violent exothermic decomposition. In this feature article, we present an alternative approach to carbene-transfer reactions based on the formation of highly electrophilic silver carbenes from N-sulfonylhydrazones, where the high electrophilicity of silver carbenes stems from the weak interaction between silver and the carbenic carbon. These precursors are readily accessible, stable, and environmentally sustainable. Using the strategy that employs highly electrophilic silver carbenes, it is possible to develop novel intermolecular transformations involving non-stabilized carbenes, including C(sp3)–H insertion, C(sp3)–C(O) insertion, cycloaddition, and defluorinative functionalization. The silver-catalyzed carbene transfer reactions described here have high efficiency, unusual reactivity, exceptional selectivity, and a reaction pathway that differs from typical transition metal-catalyzed reactions. Our research provided fundamental insight into silver carbene chemistry, and we hope to apply this mode of catalysis to other more general transformations, including asymmetric transformations. [ABSTRACT FROM AUTHOR]

Strategies on the construction of enantiomerically pure silicon‐stereogenic silanes generally relies on desymmetrization of prochiral and symmetric substrates. However, dynamic kinetic asymmetric transformations of organosilicon compounds have remained underdeveloped and unforeseen owing to a lack of an effective method for deracemization of the static silicon stereocenters. Here we report the first Rh‐catalyzed dynamic kinetic asymmetric intramolecular hydrosilylation (DyKAH) with "silicon‐centered" racemic hydrosilanes that enables the facile preparation of silicon‐stereogenic benzosiloles in good yields and excellent enantioselectivities. The special rhodium catalyst controlled by non‐diastereopure‐type mixed phosphine‐phosphoramidite ligand with axial chirality and multiple stereocenters can induce enantioselectivity efficiently in this novel DyKAH reaction. Density functional theory (DFT) calculations suggest that the amide moiety in chiral ligand plays important role in facilitating the SN2 substitution of chloride ion to realize the chiral inversion of silicon center. [ABSTRACT FROM AUTHOR]

Although there is an abundance of methods for the enantioselective synthesis of 2‐isoxazolines and 2‐isoxazolin‐5‐ones, relatively few of these approaches have been reported when these heterocycles bear fully substituted stereocenters. In this review, we will detail the methods that have been used to successfully accomplish these challenging asymmetric transformations and give insights into their importance, such as allowing access to unique three‐dimensional chemical space. The limitations of the currently known reactions will be discussed, as well as highlighting the future developments needed to advance the research field. [ABSTRACT FROM AUTHOR]

Catalytic deracemization is an ideal synthetic strategy due to its formally perfect atom utilization. Asymmetric photocatalysis has been appreciated as a promising tool to accomplish this attractive reaction pattern in an economical fashion, but it remains underdeveloped. Here, we report a new platform based on photoredox‐neutral catalysis, allowing efficient and modular optical enrichment of α‐amino esters and other valuable analogues. Two single‐electron transfer processes between the photocatalyst and the substrates serve to provide the key prochiral intermediates, and the chiral Brønsted acid catalyst mediates enantioselective protonation to reconstitute a stereogenic C−H bond. The efficiency of deracemization is determined by the enantiofacial differentiation effect during the stereocentre‐forming step. [ABSTRACT FROM AUTHOR]

Fast screening of enzyme variants is crucial for tailoring biocatalysts for the asymmetric synthesis of non-natural chiral chemicals, such as amines. However, most existing screening methods either are limited by the throughput or require specialized equipment. Herein, we report a simple, high-throughput, low-equipment dependent, and generally applicable growth selection system for engineering amine-forming or converting enzymes and apply it to improve biocatalysts belonging to three different enzyme classes. This results in (i) an amine transaminase variant with 110-fold increased specific activity for the asymmetric synthesis of the chiral amine intermediate of Linagliptin; (ii) a 270-fold improved monoamine oxidase to prepare the chiral amine intermediate of Cinacalcet by deracemization; and (iii) an ammonia lyase variant with a 26-fold increased activity in the asymmetric synthesis of a non-natural amino acid. Our growth selection system is adaptable to different enzyme classes, varying levels of enzyme activities, and thus a flexible tool for various stages of an engineering campaign. Fast screening of enzymes is key for directed evolution of industrial biocatalysts. Here, the authors report a simple, high-throughput, and low-equipment-dependent growth selection system for engineering three enzymes for synthesis of chiral amines. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: The direct conversion of unactivated alkanes and cycloalkanes into structurally diverse molecules through aliphatic C—H functionalization is a useful process, which has attracted intense interest from academia and industry. Methods to control chemo‐ and site‐selectivity, combined with asymmetric catalysis, provide appealing access to high value‐added enantiomer‐enriched compounds but are far less developed. This review focuses on recent progress in (i) asymmetric reactions of alkanes or cycloalkanes with prochiral substrates which generate a stereocenter adjacent to the cleaved C(sp3)–H bond, and (ii) C(sp3)–H enantiodiscriminatory reactions creating a new stereogenic center on the carbon of a cleaved C(sp3)–H bond. Elegant strategies are discussed, including (a) metal carbene‐induced C—H insertions by chiral rhodium catalysts, (b) metal‐oxo‐mediated C—H oxidation by biomimetic manganese catalysts, (c) enzyme catalysis by cytochromes P450 variants, and (d) dual catalysis by a photocatalyst and a chiral Lewis acid (CLA) or a chiral phosphoric acid (CPA). These catalytic systems can not only precisely recognize primary, secondary and tertiary C—H bonds at specific positions in alkanes and cycloalkanes, but also support a high level of stereoselectivity in the reactions. It is expected that the advances will stimulate further progress in asymmetric catalysis, synthetic methodology, pharmaceutical development and industrial processes. [ABSTRACT FROM AUTHOR]

Chiral primary α-amino amides, consisting of an adjacent enamine bonding site (Bronsted base site), a hydrogen bonding site (Bronsted acid site), and flexible bulky substituent groups to modify the steric factor, are proving to be extremely valuable bifunctional organocatalysts for a wide range of asymmetric organic transformations. Primary α-amino amides are less expensive alternatives to other primary amino organocatalysts, such as chiral diamines and cinchona-alkaloid-derived primary amines, as they are easy to synthesize, air-stable, and allow for the incorporation of a variety of functional groups. In recent years, we have demonstrated the catalytic use of simple primary α-amino amides and their derivatives as organocatalysts for the aldol reaction, Strecker reaction, Michael tandem reaction, allylation of aldehydes, reduction of N-Aryl mines, opening of epoxides, hydrosilylation, asymmetric hydrogen transfer, and N-specific nitrosobenzene reaction with aldehydes. [ABSTRACT FROM AUTHOR]

The Nobel Prize in Chemistry for the year 2021 was awarded to Prof. Benjamin List of Max-Planck-Institut für Kohlenforschung, Mülheim an der Ruhr, Germany and Prof. David W.C. MacMillan of Princeton University, Princeton, NJ, USA. The award was given for their contribution to developing and popularizing asymmetric organocatalysis as an efficient tool for the construction of organic molecules. Organocatalysis is the use of small organic molecules to catalyze organic reactions, which has gained attention for bringing about asymmetric transformations without the use of metal catalysts. Both Prof. List and Prof. MacMillan pioneered the activation of carbonyl compounds by converting them to iminium ions or enamines using optically active secondary amines as organocatalysis. This article will discuss the contributions of List and MacMillan with brief introductions to the problems they attempted to solve using organocatalysis. [ABSTRACT FROM AUTHOR]

Asymmetric organocatalytic reactions of various electron‐deficient racemic allenes with a wide variety of nucleophiles and electrophiles were reviewed. The literature on enantioselective functionalization of allenes that employs chiral phosphine, amine, phase transfer, bifunctional, and Brønsted acid catalysis is presented along with the mechanisms. In addition, the review emphasizes methods of obtaining enantioenriched allenes from racemic allenes via organocatalytic (dynamic) kinetic resolution techniques. The synthetic utility of the developed methodologies toward the target‐orientated biologically active molecules is narrated along with the examples. [ABSTRACT FROM AUTHOR]

Jiawang Liu, a Tenure‐track Associate Professor at Shanghai Jiao Tong University, recently published an article in Angewandte Chemie on the enantioconvergent carboxylation of racemic heterobiaryl (pseudo)halides with CO2. His research focuses on CO2/CO transformation, asymmetric catalysis, and photocatalysis. Liu's work aims to develop sustainable chemistry and explore new opportunities for CO2 asymmetric transformation by combining photocatalysis with transition metal catalysis. [Extracted from the article]

Jiawang Liu, a Tenure‐track Associate Professor at Shanghai Jiao Tong University, recently published an article in Angewandte Chemie on enantioconvergent carboxylation. His research focuses on CO2 transformation, asymmetric catalysis, and photocatalysis. Liu's work combines photocatalysis with transition metal catalysis to explore new opportunities for CO2 asymmetric transformation, addressing challenges such as product racemization. [Extracted from the article]