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N‐heterocyclic carbene (NHC) catalysis has become a versatile catalysis strategy for building molecules via unique reaction modes. Dual catalytic processes using NHCs in combination with additional modulating agents such as another organocatalyst or transition‐metal catalyst have also been studied. The clear selection of cocatalysts has led to enhanced reactivity, increased yields, and/or improved stereoselectivity. This minireview is to provide readers with a brief overview of the development and applications of NHC and hydrogen‐bond donor for dual catalytic reactions. [ABSTRACT FROM AUTHOR]

This review highlights the allylic C−H alkylation of alkenes (AAH) with nucleophiles under Pd0 or PdII catalysis and achiral or chiral conditions. The η3‐allylpalladium intermediates of these reactions are formed from the cleavage of an allylic hydrogen which becomes a leaving group, like the acetate moiety of allyl acetates during the classical Tsuji‐Trost procedure. Most of these cross‐dehydrogenative‐couplings require quinones as key components; they may play the role of ligand, proton trap and oxidant. Efficient asymmetric allylic C−H alkylations (AAAH's) have been performed. The diversity of the procedures, their limitation and application in synthesis are underlined as well as the proposed mechanisms with, in some cases, personal comments. The data are grouped according to the reaction conditions. [ABSTRACT FROM AUTHOR]

An unprecedented Cinchona alkaloid catalyzed atropoenantioselective transamination of biaryl aldehydes with 2,2-diphenylglycine via a cascade decarboxylation and dynamic kinetic resolution strategy is described. This protocol features broad substrate scope and good functional group tolerance and allows the rapid assembly of axially chiral biaryls in high yields with acceptable to good enantioselectivities. In addition, such structural motifs may have potential applications in enantioselective catalysis as chiral ligands or catalysts. [ABSTRACT FROM AUTHOR]

Copolymers are valuable supports for obtaining heterogeneous catalysts that allow their recycling and therefore substantial savings, particularly in the field of asymmetric catalysis. This contribution reports the use of two comonomers: Azido-3-propylmethacrylate (AZMA) bearing a reactive azide function was associated with 2-methoxyethyl methacrylate (MEMA), used as a spacer, for the ATRP synthesis of copolymers, and then post-functionalized with a propargyl chromium salen complex. The controlled homopolymerization of MEMA by ATRP was firstly described and proved to be more controlled in molar mass than that of AZMA for conversions up to 63%. The ATRP copolymerization of both monomers made it possible to control the molar masses and the composition, with nevertheless a slight increase in the dispersity (from 1.05 to 1.3) when the incorporation ratio of AZMA increased from 10 to 50 mol%. These copolymers were post-functionalized with chromium salen units by click chemistry and their activity was evaluated in the asymmetric ring opening of cyclohexene oxide with trimethylsilyl azide. At an equal catalytic ratio, a significant increase in enantioselectivity was obtained by using the copolymer containing the largest part of salen units, probably allowing, in this case, the more favorable bimetallic activation of both the engaged nucleophile and electrophile. Moreover, the catalytic polymer was recovered by simple filtration and re-engaged in subsequent catalytic runs, up to seven times, without loss of activity or selectivity. [ABSTRACT FROM AUTHOR]

Background: The combination of metal-catalyzed reactions and enzyme catalysis has been an essential tool for synthesizing chiral pharmaceutical intermediates in the field of drug synthesis. Metal catalysis commonly enables the highly efficient synthesis of molecular scaffolds under harsh organic conditions, whereas enzymes usually catalyze reactions in mild aqueous medium to obtain high selectivity. Since the incompatibility between metal and enzyme catalysis, there are limitations on the compatibility of reaction conditions that must be overcome. Findings: We report a chemoenzymatic cascade reaction involved Palladium (Pd) catalyzed Suzuki–Miyaura coupling and whole-cell catalyzed C = O asymmetric reduction for enantioselective synthesis of value-added chiral alcohol. The cell membrane serves as a natural barrier can protect intracellular enzymes from organic solvents. Conclusions: With dual advantages of cascade catalysis and biocompatibility, our work provides a rational strategy to harvest chiral alcohols in high yield and excellent enantioselectivity, as a channel to establish chemoenzymatic catalysis. [ABSTRACT FROM AUTHOR]

We report herein sharp physical evidence, i.e., single-crystal X-ray diffraction and 1H-NMR spectral data, confirming that quaternary ammonium species interact with anions via a set of directional ion–dipole cooperative +N-C-H unusual H-bonding interactions and not via pure non-directional ionic electrostatic interactions. This finding, which has been often invoked by calculations, is herein substantiated by the preparation of two model compounds and an analysis of their X-ray crystal structures in the solid state and 1H-NMR spectra in solution. These observations are particularly pertinent for the rational design of novel catalyses and catalysts and providing guidance to an understanding of these species in solution and during asymmetric enantioselective catalysis. [ABSTRACT FROM AUTHOR]

Molecular capsules enable the conversion of substrates inside a closed cavity, mimicking to some extent enzymatic catalysis. Chirality transfer from the molecular capsule onto the encapsulated substrate has been only studied in a few cases. Here we demonstrate that chirality transfer is possible inside a rather large molecular container of approximately 1400 Å3. Specifically, we present 1) the first examples of optically active hexameric resorcin[4]arene capsules, 2) their ability to enantioselectively catalyze tail‐to‐head terpene cyclizations, and 3) the surprisingly high sensitivity of enantioselectivity on the structural modifications. [ABSTRACT FROM AUTHOR]

A general and efficient organocatalytic asymmetric polymerization approach for the synthesis of chiral covalent organic frameworks (CCOFs) has been developed. With a chiral 2‐methylpyrrolidine catalyst, a series of tris(N‐salicylideneamine)‐derived β‐ketoenamine‐CCOFs are directly constructed from prochiral aldehyde‐ and primary amine‐monomers. The adopted aminocatalytic asymmetric Schiff‐base condensation herein is performed under ambient conditions with clear green synthetic advantages over the conventional acid‐catalysed solvothermal methods. The obtained β‐ketoenamine‐CCOFs can be further metalated by a solid‐state coordination approach, and the resulting CuII@CCOFs can highly promote an asymmetric A3‐coupling reaction. Specifically, a CuII@CCOF@chitosan aerogel was fabricated as a highly efficient fixed‐bed model reactor for scaled‐up catalysis. The concept of aminocatalytic asymmetric polymerization might open a new way for constructing the CCOFs via asymmetric organocatalysis. [ABSTRACT FROM AUTHOR]

Enantioselective, intermolecular alkene arylamination was achieved through gold redox catalysis. Screening of ligands revealed chiral P,N ligands as the optimal choice, giving alkene aminoarylation with good yields (up to 80 %) and excellent stereoselectivity (up to 99 : 1 er). As the first example of enantioselective gold redox catalysis, this work confirmed the feasibility of applying a chiral ligand at the gold(I) stage, with the stereodetermining step (SDS) at the gold(III) intermediate, thus opening up a new way to conduct gold redox catalysis with stereochemistry control. [ABSTRACT FROM AUTHOR]

We report the catalysis of an enantioselective, intramolecular aldol reaction accelerated by an organocatalyst embedded in a series of multicomponent metal‐organic frameworks. By precisely programming the pore microenvironment around the site of catalysis, we show how important features of an intramolecular aldol reaction can be tuned, such as the substrate consumption, enantioselectivity, and degree of dehydration of the products. This tunability arises from non‐covalent interactions between the reaction participants and modulator groups that occupy positions in the framework remote from the catalytic site. Further, the catalytic moiety can be switched form one framework linker to another. Deliberately building up microenvironments that can influence the outcome of reaction processes in this way is not possible in conventional homogenous catalysts but is reminiscent of enzymes. [ABSTRACT FROM AUTHOR]

The continuous flow, enantioselective, organophotoredox catalytic asymmetric alkylation of aldehydes was studied, by using a homemade, custom‐designed photoreactor for reactions under cryogenic conditions. Going from microfluidic conditions up to a 10 mL mesofluidic reactor, an increase of productivity by almost 18000 % compared to the batch reaction was demonstrated. Finally, for the first time, a stereoselective photoredox organocatalytic continuous flow reaction in a fully telescoped process for an active pharmaceutical ingredient (API)synthesis was successfully achieved. The final process consists of four units of operation: visible light‐driven asymmetric catalytic benzylation under continuous flow, inline continuous work‐up, neutralisation and a final oxidative amidation step afforded the pharmaceutically active molecule in 95 % e.e. [ABSTRACT FROM AUTHOR]

The stereoselective synthesis of molecules bearing stereogenic phosphorus(V) centers represents an enduring challenge in organic chemistry. Although stereospecific nucleophilic substitution at P(V) provides a general strategy for elaborating optically active P(V) compounds, existing methods for accessing the requisite chiral building blocks rely almost entirely on diastereocontrol using chiral auxiliaries. Catalytic, enantioselective methods for the synthesis of synthetically versatile stereogenic P(V) building blocks offer an alternative approach to stereogenic-at-P(V) targets without requiring stoichiometric quantities of chiral control elements. Here, we report an enantioselective hydrogen-bonddonor-catalyzed synthesis of aryl chlorophosphonamidates and the development of these products as versatile chiral P(V) building blocks. We demonstrate that the two leaving groups on these chlorophosphonamidates can be displaced sequentially and stereospecifically to access a wide variety of stereogenic-at-P(V) compounds featuring diverse substitution patterns. [ABSTRACT FROM AUTHOR]

Molecular recognition and self-assembly are often mediated by intermolecular forces involving aromatic π-systems. Despite the ubiquity of such interactions in biological systems and in the design of functional materials, the elusive nature of aromatic π interaction results in that they have been seldom used as a design element for promoting challenging chemical reactions. Described here is a well-engineered catalytic system into which non-covalent π interactions are directly incorporated. Enabled by a lone pair-π interaction and a π-π stacking interaction operating collectively, efficient chiral recognition is successfully achieved in the long-pursued dihydroxylation-based kinetic resolution. Density functional theory calculations shed light on the crucial role played by the lone pair-π interaction between the carbonyl oxygen of the cinchona alkaloid ligand and the electron-deficient phthalazine π moiety of the substrate in the stereoselectivity-determining transition states. This discovery serves as a proof-of-principle example showing how the weak non-covalent π interactions, if ingeniously designed, could be a powerful guide in attaining highly enantioselective catalysis. Non-covalent π interactions have been rarely used as a design element for promoting chemical reactions. Here the authors report a Sharpless asymmetric dihydroxylation (SAD)-based kinetic resolution in which a-priori-designed non-covalent forces play a central role in differentiating the enantiomeric substrates. [ABSTRACT FROM AUTHOR]

Homochiral metal-organic frameworks (MOFs) have attracted considerable attention in many fields of research, such as chiral catalysis and chiral chromatography. However, only few homochiral MOFs can be effectively used in capillary electrochromatography (CEC) and their performances are far from adequate. In this study, we successfully synthesized achiral nanocrystalline MIL-53. A facile post-synthetic modification strategy was then implemented to functionalize the product, yielding a homochiral MOF: l -His-NH-MIL-53. This MOF was then employed as a chiral coating in open-tubular CEC mode (OT-CEC), and, as such, it exhibited high enantioselectivities for several racemic drugs. The homochiral MOF and the fabricated capillary coating were systematically characterized using transmission electron microscopy, scanning electron microscopy (with energy-dispersive X-ray spectrometry), Fourier-transform infrared spectroscopy, X-ray diffractometry, thermogravimetric analysis, circular dichroism spectroscopy, Brunauer-Emmett-Teller surface area measurements, and X-ray photoelectron spectroscopy. This study is expected to provide a new strategy for the design and establishment of MOF-based chiral OT-CEC systems. [Display omitted] • l -His-NH-MIL-53 was prepared as a novel chiral stationary phase for OT-CEC. • Multiple methods were employed to characterize the MOF and MOF coating. • MOF-modified capillary exhibited high enantioselectivity for several racemic drugs. [ABSTRACT FROM AUTHOR]

Catalyst optimization for enantioselective transformations has traditionally relied on empirical evaluation of catalyst properties. Although this approach has been successful in the past it is intrinsically limited and inefficient. To address this problem, our laboratory has developed a fully informatics guided workflow to leverage the power of artificial intelligence (AI) and machine learning (ML) to accelerate the discovery and optimization of any class of catalyst for any transformation. This approach is mechanistically agnostic, but also serves as a discovery platform to identify high performing catalysts that can be subsequently investigated with physical organic methods to identify the origins of selectivity.

A procedure for the enantioselective synthesis of α-substituted glutamates and pyroglutamates via a cyclopropenimine-catalyzed Michael addition of amino ester imines is described. Enantioselectivities of up to 94% have been achieved, and a variety of functional groups were found to be compatible. The impact of the catalyst structure and imine substitution is discussed. Compared to other methods, this protocol allows for a broader and more enantioselective access to pyroglutamate derivatives.

The transition metal (palladium)-catalysed asymmetric 1,4-addition of arylboronic acids to conjugated enones belong to the most important and emerging strategies for the construction of C–C bonds in an asymmetric fashion. This review covers known catalytic systems used for this transformation. For clarity, we are using the type of ligand as a sorting criterion. Finally, we attempted to create a flowchart facilitating the selection of a suitable ligand for a given combination of enone and arylboronic acid.

The widely used combinations of palladium catalysts and chiral phosphoric acids face with the problems of cooperative catalysis and low-cost immobilization of binary catalysts in heterogeneous catalysis, due to the significant decline in the freedom of anchored catalysts. In this paper, the one-pot immobilization of both chiral phosphoric acid (TRIP) and Pd(PPh 3) 4 to hollow mesoporous polystyrene nanospheres (HMPNs) via Friedel-Crafts alkylation is developed to fabricate HMPNs-supported dual organo/metal catalysts (Pd(PPh 3) 4 #TRIP@HMPNs) at a low cost. The efficient cooperative catalysis of anchored TRIP and Pd(PPh 3) 4 with good to excellent yields (89 93 %) and enantioselectivities (80 87 % ee) is achieved in the direct asymmetric α-allylation of aldehydes with allylic alcohols. The higher molar ratio of TRIP to Pd(PPh 3) 4 and a lower crosslinking degree of HMPNs are beneficial to the cooperative catalysis of the anchored catalysts. Overall, this paper showcases a success in solving the key problems in heterogeneous asymmetric metal/oragano catalysis. [Display omitted] • Success in solving the problems in heterogeneous asymmetric metal/oragano catalysis. • One-pot covalent immobilization of dual metal catalyst and chiral organocatalyst. • Efficient heterogeneous organo/metal cooperative catalysis. • Well-shaped hollow mesoporous polystyrene nanospheres as catalyst support. [ABSTRACT FROM AUTHOR]

Chiral emulsions, with the chiral center of chiral-surfactant as the emulsifier, provide opportunities for selective catalysis and inorganic material synthesis. Janus emulsion draws researcher's attention due to excellent multiple chambers, advanced structures and diverse interfaces. Chiral Janus emulsions are prepared with two immiscible oils of vegetable oil (VO)/dimethyl phthalate (DMP) and 2-(Perfluorooctyl)ethyl methacrylate (PFOEMA)/Ethoxylated trimethylolpropane triacrylate (ETPTA) as inner phases, by emulsified by chiral-surfactant [H-G-C 16 ]FeCl 4 , in batch-scale by traditional vortex mixing. AuNPs as functional nanomaterials with peroxidase activity are then applied as active centers, adsorbing at the oil/water interface due to the electrostatic interactions between the positive charge of [H-G-C 16 ]FeCl 4 at Janus emulsion interfaces and the negative charge of AuNPs modified by SDS. Chiral Janus emulsion is endowed with catalytic activity and enantioselectivity. Catalytic results show two AuNPs@ Janus emulsions show better affinity to catalyze the oxidation of L -DOPA than D -DOPA. By investigating two AuNPs@ Janus emulsions with different inner phases, chiral Janus emulsion of AuNPs@ETPTA/PFOEMA/[H-G-C 16 ]FeCl 4(aq) has better catalytic activity and enantioselectivity than AuNPs@DMP/VO/[H-G-C 16 ]FeCl 4 (aq) because of the smaller droplets have larger interface areas could adsorb more [H-G-C 16 ]FeCl 4 molecules and AuNPs. The findings open an avenue in the production of chiral Janus emulsions with catalytic effect and enantioselectivity, which would push forward future applications in selective catalysis and inorganic material synthesis. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • Heterogeneous chiral single-Rh-site catalysis (Rh-HCSMSCs or Rh-SACs) for asymmetric transformations. • Rh-HCSMSCs was illustrated excellent classical batch recycle and a decagram scale-up asymmetric continuous-flow with high TON. • Amplification of enantioselectivity of catalysts was facilitated by polymerization process. Rhodium-catalyzed asymmetric reactions have played a pivotal role in the synthesis of functional chiral molecules. However, the ambiguous mechanism involving several plausible catalytically active species, the potential for catalyst deactivation and the need for constant reusability remain key challenges. Heterogeneous chiral Rh catalysts are highly desirable, but their performance has been hampered by low density and stability of catalytically active sites. Herein, we have devised a versatile methodology for fabricating highly efficient and robust chiral heterogeneous single-Rh-site catalysts by direct polymerization. The successful anchoring of single Rh-ligand species, the amplification of enantioselective inductive ability and the uniform distribution of atomic Rh sites within the resulting polymer matrix are identified as crucial factors contributing to their exceptional catalytic performance via comprehensive characterization and controlled experiments. In contrast to the corresponding homogeneous analogues, these chiral single-Rhodium-site catalysts exhibit outstanding performance, yielding enhanced enantioselectivity and broad applicability, even accommodating various functional groups. Remarkably, these results are achieved with just half catalyst dosage. Furthermore, their industrial potential is demonstrated through successful utilization in continuous flow processes and robust batch recycling. In future, we aim to expand the horizons of heterogeneous chiral single-metal-site catalysis, and bring us a step closer to practical asymmetric synthesis. [ABSTRACT FROM AUTHOR]

• Thermostabilized mutants of Na StyA were constructed for asymmetric epoxidation. • Mutant TM18 had a half-life 148-fold of the parental and enhanced solvent tolerance. • Mutant produced chiral epoxides up to 4-fold yield of the parental with >99 %ee. • Mutants displayed increased local rigidity and reduced residue cross-correlation motions. Chiral epoxides are one of the most versatile building blocks in organic synthesis, but the asymmetric epoxidation of unfunctionalized terminal olefins remains a challenge. Na StyA is a styrene monooxygenase from Nocardia altamirensis that functions as an enantioselective epoxygenase for terminal olefins. To improve its robustness, we investigated over 50 mutants designed via evolutionary- and energy-based approaches, and successfully identified 18 beneficial mutations, which then led to a combinatorial mutant of TM18 with drastically enhanced thermostability and solvent tolerance while retaining excellent activity and enantioselectivity. Its turnover frequency and half-life at 50 °C were increased to 5- and 148-fold of the parental. In the epoxidation of terminal olefins, TM18 achieved high product yields of over 4-fold of the parental, and excellent enantiomeric excess of 99 % to >99 % ee. The analysis of trajectory data from molecular dynamics simulations further validated that the mutations in TM18 increased its local rigidity, as inferred by RMSF and PCA analyses and through novel salt bridges formation. Furthermore, TM18 displayed reduced residue cross-correlation motions. The combined effects of these mutations result in an overall improvement in the structural and dynamic thermostability of TM18. [ABSTRACT FROM AUTHOR]

• Easily available and robust manganese (I) complexes were described and tested for asymmetric transfer hydrogenations of ketones. • A broad range of ketones were enantioselectively hydrogenated to their chiral alcohols with ee values up to 98 %. • DFT calculations and experiments highlighted the significance of remotely polar group (C = O) and controllable cycloheptanyl groups in the catalyst, resulting in enhanced activities (TON to 860) and enantiomeric excess. A family of Mn(I) catalysts containing ferrocene-based chiral PNN tridentate ligands with "aliphatic cyclic" groups is described and tested in the asymmetric transfer hydrogenations of ketones. Various ketones (52 examples), including phenylacetones, phenylpropanones, and heterocyclic substrates could be enantioselectively hydrogenated to the corresponding chiral alcohols with conversions up to 99 % and ee values up to 98 % under mild conditions. A high turnover number of 860 was achieved with a low catalyst loading (S/C = 2000). DFT calculations and control experiments highlighted the significance of remotely polar group (C = O) and cycloheptanyl groups in the catalyst, resulting in enhanced activities and enantiomeric excess (up to 98 % ee), and disclosed the stereocontrol with the assistance of an attractive aromatic π-π stacking interaction between the phenyl of a0 and ligand pyridyl rings in the catalytic process. The potential manganese intermediates involved in the catalytic cycle were analyzed. Notably, this catalytic protocol operates under mild conditions, employing low catalyst loading, and shows a potential application in the efficient synthesis of chiral alcohol pharmacophores. Easily available and robust manganese complexes have been employed as catalysts in the ATH of ketones with outstanding activity (up to 860 TON) and high enantioselectivity (up to >98 % ee) [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] The synthesis and utilization of fluorine-containing α-alkyl-α-diazoesters has been reported. Access to fluoroalkyl cyclopropanes was achieved utilizing Rh 2 (S -PTTL) 4 as a catalyst with good yields, enantioselectivities, and diastereoselectivities across a series of styrenes and α-alkyl-α-diazoesters. This study expands the accessibility of fluorine-containing building blocks for synthesis. [ABSTRACT FROM AUTHOR]

The feasibility of cooperative catalysis between chiral N‐heterocyclic carbenes and nickel in asymmetric reactions has been demonstrated convincingly. The high efficiency of this catalytic system enables the asymmetric allylic alkylation of isatin‐derived enals with allylic carbonates and [3+3] annulation with racemic vinyl epoxides to provide straightforward access to highly enantioenriched 3,3'‐disubstituted oxindoles. The great practicality of this method in organic synthesis has been showcased by facile product modification and enantioselective synthesis of the key building block to access (−)‐debromoflustramine B. [ABSTRACT FROM AUTHOR]

Reactions of RhCl3 and (S,S)‐1,2‐diphenylethylenediamine (S,S‐dpen) in DMSO at 140 °C give Λ‐[Rh(S,S‐dpen)3]3+3Cl− (Λ‐(S,S)‐43+3Cl−) in 76 % yield. When CH2Cl2/water suspensions are treated with 1.0 equiv. of Na+ B(C6F5)4− or Na+ B(3,5‐C6H3(CF3)2)4−, the mixed salts Λ‐(S,S)‐43+2Cl−B(aryl)4− can be isolated from the organic layers (95–91 %). A wide variety of mixed and non‐mixed salts involving these and other anions (BF4−, ClO4−, I−) are also prepared. The lipophilic salts are highly enantioselective catalysts for the Michael addition of dimethylmalonate to trans‐ß‐nitrostyrene (acetone, 0 °C; 92–85 % ee). The crystal structures of seven solvated salts are determined, and hydrogen bonding between the trications and anions or solvate molecules analyzed. There is a notable affinity of chloride anions for the C3 face of Λ‐(S,S)‐43+, which features three synperiplanar NH groups. Λ‐(S,S)‐43+2I−B(C6F5)4− is an excellent chiral solvating agent for determining enantiomeric purities of chiral organic molecules with hydrogen bond accepting functional groups (11 mol% (average), CDCl3). [ABSTRACT FROM AUTHOR]

The enantioselective construction of fluorohydrins featuring a tetrasubstituted stereocenter embedded in complex frameworks represents an important challenge. Herein, we report a multicatalytic strategy enabling the stereoselective preparation of a new type of scaffold containing such a challenging fluorohydrin motif. The sequence is based on an organocatalyzed fluorination of α‐disubstituted aldehydes followed by a diastereoselective copper‐catalyzed decarboxylative aldol reaction. Reduction of the generated β‐hydroxy ketone followed by a Lewis base‐catalyzed kinetic resolution enables the isolation of original fluorinated 1,3‐diols with perfect diastereo‐ and enantio‐control. [ABSTRACT FROM AUTHOR]

In this work, we would like to present the development of a highly optimized method for generating the quaternary stereogenic centers in β-keto esters. This enantioselective phase-transfer alkylation catalyzed by hybrid Cinchona catalysts allows for the efficient generation of the optically active products with excellent enantioselectivity, using only 1 mol% of the catalyst. The vast majority of phase-transfer catalysts in asymmetric synthesis work by creating ionic pairs with the nucleophile-attacking anionic substrate. Therefore, it is a sensible approach to search for new methodologies capable of introducing functional groups into the precursor's structure, maintaining high yields and enantiomeric purity. [ABSTRACT FROM AUTHOR]

Axially chiral aldehydes have received increasing attention in enantioselective catalysis. However, only very few catalytic methods have been developed to construct structurally diverse axially chiral aldehydes. We herein describe an NHC‐catalyzed atroposelective esterification of biaryl dialdehydes as a general and practical strategy for the construction of axially chiral aldehydes. Mechanistic studies indicate that coupling proceeds through a novel combination of NHC‐catalyzed desymmetrization of the dialdehydes and kinetic resolution. This protocol features excellent enantioselectivity, mild conditions, good functional‐group tolerance, and applicability to late‐stage functionalization and provides a modular platform for the synthesis of axially chiral aldehydes and their derivatives. [ABSTRACT FROM AUTHOR]

The first chiral helicene‐NHC gold(I) complexes efficient in enantioselective catalysis were prepared. The L‐shaped chiral ligand is composed of an imidazo[1,5‐a]pyridin‐3‐ylidene (IPy) scaffold laterally substituted by a configurationally stable [5]‐helicenoid unit. The chiral information was introduced in a key post‐functionalization step of a NHC‐gold(I) complex bearing a symmetrical anionic fluoreno[5]helicene substituent, leading to a racemic mixture of complexes featuring three correlated elements of chirality, namely central, axial and helical chirality. After HPLC enantiomeric resolution, X‐ray crystallography and theoretical calculations enabled structural and stereochemical characterization of these configurationally stable NHC‐gold(I) complexes. The high potential in asymmetric catalysis is demonstrated in the benchmark cycloisomerization of N‐tethered 1,6‐enynes with up to 95 : 5 er. [ABSTRACT FROM AUTHOR]

An asymmetric allylic C−H functionalization has been developed by making use of transient chiral nucleophiles, as well as bimetallic synergistic catalysis with an achiral Pd0catalyst and a chiral N,N′‐dioxide‐CoIIcomplex. A variety of β‐ketoesters and N‐Boc oxindoles coupled with allylbenzenes and aliphatic terminal alkenes were well tolerated, furnishing the desired allylic alkylation products in high yields (up to 99 %) with excellent regioselectivities and enantioselectivities (up to 99 % ee). [ABSTRACT FROM AUTHOR]

The synthesis of small organic molecules with a difluoromethylated stereocenter is particularly attractive in drug discovery. Herein, we have developed an efficient method for the direct generation of difluoromethylated stereocenters through Ni0‐catalyzed regio‐ and enantioselective hydrosilylation of gem‐difluoroalkenes. The reaction also represents the enantioselective construction of carbon(sp3)−silicon bonds with nickel catalysis, which provides an atom‐ and step‐economical synthesis route of high‐value optically active α‐difluoromethylsilanes. This protocol features readily available starting materials and commercial chiral catalysis, broad substrates spanning a range of functional groups with high yield (up to 99 % yield) and excellent enantioselectivity (up to 96 % ee). The enantioenriched products undergo a variety of stereospecific transformations. Preliminary mechanistic studies were performed. [ABSTRACT FROM AUTHOR]

Chiral hydrogen‐bonding (H‐bonding) catalytic asymmetric conjugate addition to activated olefins has been widely used to access enantioenriched molecules containing stereocenters at the β‐position of the olefin activating groups. Herein, we report the first highly enantioselective radical‐based manifold. Under a dual organocatalyst system involving a chiral phosphoric acid and DPZ as the photoredox sensitizer, transformations of N‐arylglycines, in which aryls with CF3 substituents are introduced, with alkenyl azaarenes afforded valuable hydroaminoalkylation adducts with satisfactory results. In addition to the diversity of azaarenes, the method can be used to construct aryl‐, alkyl‐ and silyl‐substituted stereocenter. Control experiments and density functional theory calculations were performed to elucidate a plausible reaction mechanism and the origin of stereoselectivity, wherein nonclassical H‐bonding interactions were found to assist chiral catalysts in offering sufficient enantiocontrol. [ABSTRACT FROM AUTHOR]

The combination of biocatalysis and transition‐metal catalysis can complement synthetic gaps only in a chemical or biological process. However, the intrinsic mutual deactivation between enzymatic and chemical species is a significant challenge in a single operation. To address the above issue, we developed an encapsulated Au/carbene combined with a free amine dehydrogenase as a co‐catalyst system that enables an efficient hydration/amination enantioselective cascade process to be accomplished. The mechanistic investigation discloses dual catalysis comprised of alkyne hydration, followed by a reductive amination process. [ABSTRACT FROM AUTHOR]

L-phenylglycine (L-phg) is a valuable non-proteinogenic amino acid used as a precursor to β-lactam antibiotics, antitumor agent taxol and many other pharmaceuticals. L-phg synthesis through microbial bioconversion allows for high enantioselectivity and sustainable production, which will be of great commercial and environmental value compared with organic synthesis methods. In this work, an L-phg synthesis pathway was built in Escherichia coli resulting in 0.23 mM L-phg production from 10 mM L-phenylalanine. Then, new hydroxymandelate synthases and hydroxymandelate oxidases were applied in the L-phg synthesis leading to a 5-fold increase in Lphg production. To address 2-oxoglutarate, NH4+, and NADH shortage, a cofactor self-sufficient system was introduced, which converted by-product L-glutamate and NAD+ to these three cofactors simultaneously. In this way, L-phg increased 2.5-fold to 2.82 mM. Additionally, in order to reduce the loss of these three cofactors, a protein scaffold between synthesis pathway and cofactor regeneration modular was built, which further improved the L-phg production to 3.72 mM with a yield of 0.34 g/g L-phe. This work illustrated a strategy applying for whole-cell biocatalyst converting amino acid to its value-added chiral amine in a cofactor selfsufficient manner. [ABSTRACT FROM AUTHOR]

An extensive introduction is provided for the non‐expert regarding enantioselective, amine catalyzed, aldol reactions (Sections 1–3). There, a broad perspective is provided regarding: methodology limitations, mechanism, in‐water versus on‐water definitions and their theoretical basis, small‐ and large‐scale physical‐mechanical aspects, solid versus liquid starting material considerations, reproducibility, ball milling, diketone substrates, etc. The thematic emphasis then turns to practical outcomes for the reaction of nineteen aliphatic, cyclic, and aromatic ketones with 4‐nitrobenzaldehyde and benzaldehyde prior to 2021. In doing so, 172 catalysts are highlighted. The ketone substrates are listed in the Table of Contents (Section 4) and their structures are shown in Figure 1. Each ketone is summarized by a: (i) schematic, (ii) text summary, (iii) catalyst Figures, and (iv) tabular reaction/product data. Individual ketone summaries, at times, represent the distillation of over six hundred and fifty research articles, and the data refinement and its tabular reconstitution is not reproducible using a chemical database search with filters. In the review's broadest use, the Figure 1 ketone structures serve as templates to extrapolate to hypothetical substrates holding more functionality, but of related steric and electronic similarity. This pseudo matching permits a rapid answer to, "Does this methodology suit the ketone substrate at hand or not?" In a positive outcome, the best reaction conditions (stoichiometry, catalyst structure and loading, solvent, time, etc.) to affect aldol product formation (yield, dr, and ee) are delineated. A second envisioned use, allows the directed construction of diketone substrates (after viewing the tabularized data of Section 4) capable of undergoing regioselective mono‐aldol product formation. This ketone regioselectivity tactic, reacting one carbonyl moiety while the other remains unreacted, avoids ketone protection‐deprotection, and is demonstrated for the advantageous synthesis of an Alzheimer drug candidate. [ABSTRACT FROM AUTHOR]

The Schiff base and its metal complexes are extensively studied for their adaptable metal chelating properties. Their ability to alter the design and modify it for various organic and biological applications makes them versatile compounds. The chiral Schiff base and their metal complexes possess excellent stability in very high temperatures, making them a suitable candidate for organocatalysts in reactions involving harsh conditions. Besides, these chiral complexes of Schiff base can transform their chirality in the final product formed in different chemical reactions. This stereo‐induction by the chiral metal complexes of Schiff base is considerably valuable for synthesizing high optically active compounds in the field of medicinal and natural product synthesis. Thus, this review emphasizes the latest and relevant literature concerning the asymmetric catalysis of chiral Schiff base ligand‐metal complexes in various synthetic organic transformation reactions. The synthesis and the catalytic mechanisms of various reactions are discussed, including their enantioselectivities, diastereoselectivities, regioselectivities, and stereoselectivities of different complexes to organic transformation. [ABSTRACT FROM AUTHOR]

"Chirality" governs many fundamental properties in chemistry and biochemistry. While early investigations on stereochemistry are primarily dedicated to static chirality, there is an increasing interest in the field of dynamic chirality (chiral switches). These chiral switches are essential in controlling the directionality in molecular motors. Dynamic chiralities are equally crucial in switchable stereoselectivity, switchable asymmetric catalysis and enantioselective separation. Herein, we limit our discussion to recent advances on stimuli‐induced chiroptical switching of axial, helical, and planar chirality in response to external stimuli. We also discuss a few examples of applications of the switchable chirality. [ABSTRACT FROM AUTHOR]

Chiral alkaline metal Brønsted bases are traditional and reliable promoters in enantioselective catalysis. Here, new chiral potassium strong base catalysts were developed for enantioselective carbon–carbon bond-forming reactions of weakly acidic carbon pronucleophiles. Chiral potassium amide or alkyl potassium catalyzed enantioselective addition reactions to imines or α,β-unsaturated amides with good to high enantioselectivities. The good potential of chiral potassium Brønsted bases to act as proton transfer catalysts has been shown. [ABSTRACT FROM AUTHOR]

An enantioselective domino process for the synthesis of substituted 1,2‐dihydronaphthalenes has been developed by the combination of chiral amines and a bidentate Lewis acid in an orthogonal catalysis. This new method is based on an inverse electron‐demand Diels−Alder and a subsequent group exchange reaction. An enamine is generated in situ from an aldehyde and a chiral secondary amine catalyst that reacts with phthalazine, activated by the coordination to a bidentate Lewis acid catalyst. The absolute configuration of the product is controlled by chiral information provided by the amine. The formed ortho‐quinodimethane intermediate is then transformed via a group exchange reaction with thiols. The new method shows a broad scope and tolerates a wide range of functional groups with enantiomeric ratios up to 91 : 9. All‐in‐all, this enantioselective synthesis tool provides an easy access to complex 1,2‐dihydronaphthalenes starting from readily available phthalazine, aldehydes and thiols in a combinatorial way. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Under the catalysis of chiral Cu(II) complex, C2 and C3 alkylation of pyrrole and C3 alkylation of indole were realized simultaneously. The chiral oxindole skeleton with an all‐carbon quaternary stereogenic center at the C3‐position could be obtained exclusively with high yields (up to 95%) and excellent enantioselectivities (up to > 99%). [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Catalytic enantioselective ring‐opening of oxa‐ and aza‐bicyclic alkenes with readily available accessible alkenylboronic acids, promoted by a chiral phosphine–Co complex, is reported. Such a process represents the unprecedented Co‐catalyzed introduction of various alkenyl groups onto the oxa‐ and aza‐bicyclic alkenes, affording a wide range of multisubstituted functionalized cyclohexenes in up to 98% yield and 99.5 : 0.5 er. [ABSTRACT FROM AUTHOR]

Michael addition of P-H compounds, such as phosphanes, phosphane oxides and phosphonates, is a practical tool to form P-C bonds. The stereochemistry of the newly formed compounds can be influenced either by using chiral starting materials or chiral catalysts. Since the former method is limited to the readily available opticallyactive derivatives, catalytic options are more common. Enantioenriched P-C compounds can have biological activity; therefore, they are pharmaceutically valuable molecules. In this paper, an overview is provided on the conjugate addition of P-H compounds according to the type of the phosphorus derivatives. [ABSTRACT FROM AUTHOR]

A strategy for the immobilization of chiral 2,3‐bisaminocyclopropenium salt (pre‐catalyst) onto polystyrene and silica supports is presented together with a suitable procedure for the conversion into the corresponding cyclopropenimine superbase catalysts. The activity and recyclability of polystyrene‐ and silica‐supported cyclopropenimines were initially tested under batch conditions in a model Michael addition detecting comparable efficiencies but a superior stability of the latter heterogeneous catalyst (5 cycles, accumulated TON of 27.1). The preferred silica‐supported cyclopropenimine behaved very similarly to the soluble counterpart in the reaction of glycine imine with different Michael acceptors (48–92% yield; 60–98% ee) and it could be utilized as packing material for the fabrication of fixed‐bed mesoreactors (pressure‐resistant stainless‐steel columns). Continuous‐flow experiments were performed with satisfactory long‐term stability (24 h on stream) with unaltered conversion efficiency and enantioselectivity. [ABSTRACT FROM AUTHOR]

The combination of a peptide catalyst and a gold catalyst is presented for enantioselective addition reactions between branched aldehydes and allenamides. The two catalysts act in concert to provide γ,δ‐enamide aldehydes bearing a fully substituted, benzylic stereogenic center – a structural motif common in many natural products and therapeutically active compounds – with good yields and enantioselectivities. The reaction tolerates a variety of alkyl and alkoxy substituted aldehydes and the products can be elaborated into several chiral building blocks bearing either 1,4‐ or 1,5‐ functional group relationships. Mechanistic studies showed that the conformational features of the peptide are important for both the catalytic efficiency and stereochemistry, while a balance of acid/base additives is key for ensuring formation of the desired product over undesired side reactions. [ABSTRACT FROM AUTHOR]

Enantioenriched α-aryl carbonyl compounds are ubiquitous in natural products and biologically active compounds. Their synthesis has been explored over the last few decades and several methods now exist that allow for the enantioselective formation of a C(sp3)-C(sp2) bond in the α-position to a carbonyl group. However, although the formation of quaternary stereocenters has been fairly well established, the enantioselective formation of tertiary stereocenters proved more challenging due to facile product post-reaction racemization. In this short review, we summarize the methods reported to date for the asymmetric α-arylation of enolates and analogues that rely on transition-metal catalysis. 1 Introduction 2 Nucleophile Pre-activation 3 Activation via Aminocatalysis 4 Formation of Constrained Stereocenters 5 Concluding Remarks [ABSTRACT FROM AUTHOR]

The enantioselective generation of quaternary carbon centers remains challenging but is of growing importance for the preparation of functional molecules. Metal catalyzed allylic alkylations of tertiary electrophiles can provide access to these substructures but remain generally incompatible with organometallic benzyl nucleophiles. Here we demonstrate that electron‐deficient arylacetates can serve as benzyl nucleophile surrogates to generate enantioenriched acyclic molecules containing a quaternary carbon center via a two‐step substitution–decarboxylation process using isoprene monoxide. Products are often obtained in >90 % ee using a commercially available catalyst. An array of electron‐withdrawing functional groups on the arylacetate moiety are tolerated. The lactone generated by the initial substitution reaction can be used in further stereoselective transformations to prepare molecules with acyclic vicinal quaternary stereocenters. [ABSTRACT FROM AUTHOR]

Chiral organoboronates have played a critical role in organic chemistry and in the development of materials science and pharmaceuticals. Much effort has been devoted to exploring synthetic methodologies for the preparation of these compounds during the past few decades. Among the known methods, asymmetric catalysis has emerged as a practical and highly efficient strategy for their straightforward preparation, and recent years have witnessed remarkable advances in this respect. Approaches such as asymmetric borylative addition, asymmetric allylic borylation and stereospecific cross-coupling borylation, have been extensively explored and well established employing transition-metal catalysis with a chiral ligand. This review provides a comprehensive overview of transition metal-catalysed asymmetric borylation processes to construct carbon–boron, carbon–carbon, and other carbon–heteroatom bonds. It summarises a range of recent achievements in this area of research, with considerable attention devoted to the reaction modes and the mechanisms involved. [ABSTRACT FROM AUTHOR]

Microemulsions provide a unique opportunity to tailor the polarity and liquid confinement in asymmetric catalysis via nanoscale polar and nonpolar domains separated by a surfactant film. For chiral diene Rh complexes, the influence of counterion and surfactant film on the catalytic activity and enantioselectivity remained elusive. To explore this issue chiral norbornadiene Rh(X) complexes (X=OTf, OTs, OAc, PO2F2) were synthesized and characterized by X‐ray crystallography and theoretical calculations. These complexes were used in Rh‐catalyzed 1,2‐additions of phenylboroxine to N‐tosylimine in microemulsions stabilized either exclusively by n‐octyl‐β‐D‐glucopyranoside (C8G1) or a C8G1‐film doped with anionic or cationic surfactants (AOT, SDS and DTAB). The Rh(OAc) complex showed the largest dependence on the composition of the microemulsion, yielding up to 59 % (90 %ee) for the surfactant film doped with 5 wt% of AOT as compared to 52 % (58 %ee) for neat C8G1 at constant surfactant concentration. Larger domains, determined by SAXS analysis, enabled further increase in yield and selectivity while the reaction rate almost remained constant according to kinetic studies. [ABSTRACT FROM AUTHOR]

Metal‐organic frameworks (MOFs) with absolute structures are of particular interest as the asymmetry of their crystal structures enables wide applications from asymmetric catalysis to enantioselective separation. Previous reports on the synthetic strategies toward MOFs with absolute structures always required the use of chiral precursors or chiral templates, however, it is not always easy to obtain enantiopure starting materials. Here in, we report a new non‐centrosymmetric MOF, MOF‐829, synthesized from aluminium salt and achiral organic linker. Further comparisons are made between MOF‐829 and a reported Al‐based chiral MOF (MOF‐520) that is composed of the same metal ion and linker, and similarly synthesized without using chiral compounds. The configurations of the building units, the absolute structures of both MOFs, and their topologies were investigated in detail. We found that (i) topology is one of the determining factors in the formation of non‐centrosymmetric MOFs; (ii) the formation of chiral MOFs further requires the directionality of chiral linkers but more importantly chiral secondary building units (SBUs), which can be realized by fine tuning of the synthetic conditions. We envision that both synthetic exploration of chiral SBUs and the design of non‐centrosymmetric topologies will open a new direction in the design of MOFs with absolute structures. [ABSTRACT FROM AUTHOR]