Confluence of asymmetric catalysis and electrosynthesis in sustainable chemical transformations

Electrosynthesis has gained widespread recognition for its extraordinary ability to precisely control the redox process.This outstanding capability enables the direct conversion of non-functionalized substrates into reactive intermediates by utilizing easily accessible starting materials, eliminating the need for preliminary functionalization procedures and allowing for unconventional bond activations.

Recent Progress of Asymmetric Catalysis from a Chinese Perspective

The precise construction of chiral molecules is a core research area in chemical science and technology.Among the plethora of reported synthetic methods,asymmetric catalysis has emerged as one of the most efficient and direct ways to obtain optically pure chiral compounds.This article mainly reviews the recent progress of asymmetric catalysis made by Chinese chemists from the following aspects:the development of new chiral ligands,transition metal-catalyzed asymmetric reactions,asymmetric organocatalytic reactions,and new strategies for asymmetric catalysis.This review does not intend to be comprehensive;only representative examples are selected to highlight the important progress made in this field.Finally,a brief outlook is given on the development of novel chiral ligands/catalysts,new enantioselective reactions,and their applications in chiral drugs and agricultural chemicals.

Feng Ligand:Privileged Chiral Ligand in Asymmetric Catalysis

Catalysts and ligands possessing the great ability to tolerate over a wide range of mechanistically unrelated reactions are remarked as"privileged",which are rather scarce but extremely meaningful in asymmetric catalysis.Feng and co-workers have developed a library of conformationally flexible,C2-symmetric N,N'-dioxide amide compounds with original design and featured structure(named as Feng ligand now).They were initially reported as chiral organocatalysts in 2005 and have been further developed as a new class of privileged chiral ligands since 2006.Tremendous success,including versatile coordination chemistry with plenty of metal sources(main-group metals,transition metals,and rare-earth metals),a truly broad scope of asymmetric reactions(more than 50 types),diverse areas of catalysis(organocatalysis,Lewis-acid catalysis,bimetallic relay catalysis,and photocatalysis),numerous synthetic applications of bioactive compounds,has been achieved using Feng N,N'-dioxide.Besides,they demonstrate that chiral ligands with conformationally flexible property can offer excellent chiral environment as well,which challenges the conventional idea preferring rigid structures in the design of chiral ligands.Herein,we briefly introduced the discovery of Feng ligand and the millstones during the development.We also covered the successful applications of Feng ligand by other scientists as well as novel chiral ligands inspired by them.

Chiral covalent organic frameworks for asymmetric catalysis and chiral separation

Covalent organic frameworks(COFs), covalently assembled from the condensation reactions of organic building blocks, are a fascinating class of functional porous materials with two-or three-dimensional crystalline organic structures. Generally, it is preferable to use symmetric and rigid building blocks to construct highly crystalline COFs with desired topology. On the other hand, the incorporation of chiral functional moieties in the building blocks would open up new applications such as asymmetric catalysis and chiral separation. This mini review highlights the principle strategies in the design and synthesis of chiral COFs. The interesting and potential applications of these chiral COFs for asymmetric catalysis and chiral separation are also summarized.This mini review aims to provide an up-to-date advancement of chiral COFs for asymmetric catalysis and chiral separation.

Asymmetric photocatalysis over robust covalent organic frameworks with tetrahydroquinoline linkage

The asymmetric photocatalytic organic synthesis(APOS)process is a sustainable and environmentally benign method for the production of optically active chemicals with sunlight as an energy source.However,it still lacks efficient semiconductors with tunable band structures and has a low recycling stability.Herein,we report the synthesis of tetrahydroquinoline-linked covalent organic frameworks(QH-COFs)with irreversible tetrahydroquinoline linkage as efficient semiconductors for the visible-light-driven asymmetricα-alkylation of aldehydes by merging with a chiral secondary amine.Up to 94%ee was obtained over QH-COFs,and the activity of QH-COFs was significantly higher than those of inorganic semiconductors(e.g.,Ti O2,Bi VO4,and WO3)under similar conditions,which is mainly attributed to their narrow band gap and suitable band edge.As far as we know,QH-COFs are the most active semiconductors for asymmetricα-alkylation of aldehydes ever reported.The QH-COFs were prepared via a one-pot Povarov cascade imine formation and cycloaddition reaction using Sc(OTf)3/Yb(OTf)3 as Lewis acid catalysts.Attributed to the tetrahydroquinoline linkage,QH-COFs showed extremely high recycling stability,which made practicals application possible.This work not only opens up a new avenue for asymmetric photocatalysis but also provides an efficient and general method for the construction of robust COFs.

The synthesis of tetracyclic coumarins via decarboxylative asymmetric[4+2]cycloadditions enabled by Pd(0)/Cu(I)synergistic catalysis

Tetracyclic coumarins are a class of important compounds with diverse and superior pharmacolog‐ical activities.However,a direct stereoselective method from simple and readily‐made coumarins derivatives remains challenging due to the inertness of coumarins as dienophiles.Herein,we de‐velop a decarboxylative asymmetric[4+2]cycloaddition of 3‐cyanocoumarins with vinyl benzoxa‐zinones,affording the coumarin‐derived condensed rings bearing three continuous stereocenters in high yields with excellent diastereoselectivities(>20/1 d.r.)and enantioselectivities(up to 99%ee).This direct enantioselective reaction was achieved by a Pd(0)/Cu(I)bimetallic catalytic system.The mechanism studies indicated that the synergistic activation effect,in which chiral Cu(I)as an availa‐ble Lewis acid catalyst activates 3‐cyanocoumarin and chiral Pd(0)complex activates benzoxazi‐none by the formation ofπ‐allyl‐palladium intermediate,plays an important role on the stereoselec‐tive control.The current work provides a new activation modes of Cu catalyst in the Pd/Cu bimetal‐lic catalytic system.

Recent advances in the total synthesis of monoterpenoid indole alkaloids enabled by asymmetric catalysis

Asymmetric catalysis has continued to enable the preparation of optically active natural products over the past decade.This minireview summarizes progress in the catalytic enantioselective total synthesis of complex monoterpenoid indole alkaloids covering the reports from 2019 to June 2021.In particular,the generation of the key chiral stereogenic centers with metal catalysts and organocatalysts has been highlighted,showcasing the power of asymmetric catalysis protocols in accessing complex molecular architectures.

Asymmetric catalysis in synthetic strategies for chiral benzothiazepines

Chiral benzothiazepines constitute the core structures of many foremost pharmaceuticals with diverse biological activities endowed by their unique scaffolds,which poses a great challenge to organic chemists and pharmaceutical researchers.This review provides a concise overview for the asymmetric synthesis of chiral benzothiazepine derivatives,focusing on advances in asymmetric catalysis,including metal catalysis,small-molecule organocatalysis and enzymatic catalysis.The catalytic asymmetric reactions,involving asymmetric epoxidation,reduction,dihydroxylation,hydrogenation,aldol reaction and other sulfa-Michael addition,have emerged as powerful strategies for the rapid construction of chiral benzothiazepine through single or multistep reactions.The booming asymmetric synthetic methodology affords us instructive clues for the highly efficient preparation of chiral benzothiazepines,facilitating their large-scale preparation and diversity-oriented synthesis.

Operationally Simple Enantioselective Silane Reduction of Ketones by the [Ir(OMe)(cod)]2/Azolium Catalytic System

An operationally simple protocol was designed for the enantioselective silane reduction (ESR) of ketones using air- and moisture-stable [Ir(OMe)(cod)]2 (cod = 1,5-cyclooctadiene) (3) as a metal catalyst precursor. This reaction was driven by chiral hydroxyamide-functionalized azolium salt 2. The catalytic ESR reaction could be performed under benchtop conditions at room temperature. Treatment of 2 with 3 in THF yielded the monodentate IrCl(NHC)(cod) (NHC = N-heterocyclic carbene) complex 4 in 93% yield, herein the anionic methoxy ligand of 3 serves as an internal base that deprotonates the azolium ring of 2. The well-defined Ir complex 4 catalyzed the ESR reaction of propiophenone (6) with (EtO)2MeSiH using the pre-mixing reaction procedure. Based on this success, the catalytic ESR reaction was designed and implemented using an in situ-generated NHC/Ir catalyst derived from 2 and 3. Thus, a wide variety of aryl ketones could be reduced to the corresponding optically active alcohols in moderate to excellent stereoselectivities at room temperature without temperature control. Since the high catalytic activity of 3 was observed, we next evaluated several other transition metal catalyst precursors for the catalytic ESR reaction under the influence of 2. This evaluation revealed that Ir(acac)(cod) (acac = acetylacetonate) (28) and [IrCl(cod)]2 (5) can be successfully used as metal catalyst precursors in the ESR reaction.

New strategies for asymmetric photocatalysis: asymmetric organocatalytic/photoredox relay catalysis for efficient synthesis of polycyclic compounds containing vicinal amino alcohols

An asymmetric catalytic strategy in photocatalysis utilizing a chirality-induced approach through an organocatalytic/photoredox relay catalysis strategy is successfully achieved for the rapid construction of polycyclic compounds containing vicinal amino alcohols in a one-pot protocol. This methodology facilitates the efficient synthesis of diverse substituted polycyclic tetrahydroquinoline and benzofuran-derived vicinal amino alcohols, each containing five consecutive chiral centers, with high yields,excellent diastereoselectivities and enantioselectivities(up to 95% yield, >20:1 dr and 98% ee), under mild reaction conditions driven by sequential bifunctional squaramide organocatalyst-catalyzed [4+2] annulation and photocatalyst-catalyzed ketyl radical addition cyclization reaction process. Furthermore, investigations into the stereoselectivity mechanism and high-resolution mass spectrometry(HRMS) experiments on free radical trapping have provided evidence for elucidating the detailed mechanism of chirality-induced processes and chiral intermediate conversions in this procedure.

Development of efficient solid chiral catalysts with designable linkage for asymmetric transfer hydrogenation of quinoline derivatives

Developing chiral solid catalysts for asymmetric catalysis is desirable for the elimination of homogeneous catalysis flaws but remains an immense challenge.Herein,we report the immobilization of TsDPEN on SBA‐15 with an ionic liquid(IL)linkage via the one‐pot reaction of imidazole‐TsDPEN‐N‐Boc with 3‐(trimethoxysilyl)propyl bromide in the SBA‐15 mesopores.After coordination to Rh,the chiral solid catalysts could efficiently catalyze quinoline transfer hydrogenation,achieving 97%conversion with 93%ee,which was comparable to their homogeneous counterparts.The chiral solid catalyst with the IL linkage afforded much higher turnover frequency than that without the IL linkage(93 h^(–1)vs.33 h^(–1)),attributed to the phase transfer and formate‐enriching ability of the IL linkage.Furthermore,the effect of the pH on the reaction rate of the solid catalyst was investigated,preventing reaction rate retardation during the catalytic process.The tuning of the linkage group is an efficient approach for catalytic activity improvement of immobilized chiral catalysts.

Immobilizing BINOL via Suzuki Reaction:Synthesis and Application in Catalytic Asymmetric Oxidation of Sulfide to Sulfoxide

Immobilizing chiral 1,1＇-bi-2-naphthol （BINOL） in one step onto polymer backbone via stable carbon-carbon bond through Suzuki reaction was achieved. The application of this immobilized chiral BINOL to the catalytic asymmetric oxidation of sulfide to sulfoxide exhibited good activity （up to 60% yield） and high enantioselectivity （up to 89% ee）. The immobilized chiral catalyst was very stable and could be readily reused for over 5 times without significant loss of catalytic activity and enantioselectivity.

Asymmetric Catalytic Hydrogenation Using Rhodium Diphosphinites Derived From D-glucose and D-mannitol

Three diphosphinites were synthesized for preparing rhodium-diphosphinite complexes. The complexes were used for asymmetric catalytic hydrogenation of amino acid precursor alpha-acetamidocinnamic acid and its methyl ester. With all complexes, D-amino acid is the most abundant product.

Synthesis,Crystal Structure and Heterogeneous Catalysis of a New Chiral Manganese Coordination Polymer Based on the Schiff-base Ligand

A homochrial manganese（Ⅲ） complex（1） derived from chiral salen ligand（1 R,2 R）-（-）-1,2-diphenylethane-1,2-diamine-N,N？-bicarboxyl-salicylidene） has been synthesized through solvothermal procedure and characterized by IR,elemental analysis,TGA,circular dichroism（CD）,powder and single-crystal X-ray crystallography.It crystallizes in orthorhombic,space group P212121 with a = 9.108（3）,b = 16.431（5）,c = 26.531（6） A,V = 3970.4（19） A^3,Z = 4,Dc = 1.248 g/cm^3,F（000） = 1568,Mr = 745.73,μ = 0.383 mm^-1,the final GOOF = 0.957,R = 0.0631 and wR = 0.1079 for 13250 observed reflections with I 〉 2σ（I）.The coordination polymer 1 possesses a 1 D infinite zigzag chain architecture constructed by the dicarboxyl-functionalized metallosalen ligand（Mn-salen）,and the polymeric chains are further assembled into a 3D supramolecular network structure via strong intermolecular hydrogen bonding interactions between adjacent zigzag chains.As a heterogeneous catalyst,1 was used as an efficient heterogeneous catalyst for the asymmetric olefin epoxidation.

Novel Fréchet-type dendritic BINOL ligands and their applications in Ti(IV) complex catalyzed asymmetric addition of diethylzinc to aldehydes

New Frechet-type dendritic BINOL ligands bearing several BINOL units at the periphery have been successfully synthesized. The （dendritic BINOL） Ti（IV） complexes were proved to be efficient catalysts for the enantioselective addition of diethylzinc to aromatic aldehydes. Moreover, these ligands could be quantitatively recovered and reused at least five times without a loss of the yield and enantioselectivity.

Design and synthesis of chiral Ti-1,1′-bi-2-naphthol coordination polymers for heterogeneous catalytic asymmetric oxidation of sulfides

Polymer-immobilized catalysis has many advantages such as easy recovery and reuse of catalyst. We prepared three novel chiral 1,1＇-bi-2-naphthol-Ti coordination polymers with properly designed ligands and Ti（O^ipr）4 under mild conditions. The prepared polymers exhibited good activity and excellent enantioselectivity （over 99%ee） in catalyzing the asymmetric oxidation of sulfides. The bridge linker in the polymer and the reaction solvent noticeably affected the enantioseleetivity. The chiral coordination polymer was very stable and easy to separate from catalyzed reaction systems, with no significant loss of activity or enantioselectivity after reuse for at least ten times. These findings suggest a promising type of catalysts for synthesizing the widely used sulfoxides by asymmetrically oxidizing sulfides.

Asymmetric annulations based on cycloisomerization of cyclopropyl tethered allenyl ketones by bimetallic relay catalysis

The diastereo-and enantioselective tandem cycloisomerization/[4+2]-cycloaddition reaction of cyclopropyl tethered allenyl ketones withα,β-unsaturated carbonyl compounds was realized firstly under mild reaction conditions by using bimetallic silver(I)/chiral metal-N,N′-dioxide catalysts,providing a facile and atom-economic route to enantioenriched polysubstituted furopyran derivatives with good results.Possible transition state models were proposed to explain the stereoinduction.

Chiral Phenol-2NO Ligand Cooperation with Achiral Organic Base in the Zn(II)-Catalyzed Asymmetric Alkylation Reaction of Indoles

The privileged C_(2)-symmetric rigid phenol-type ligand is more attractive but challenging in asymmetric catalysis.Herein,we designed and synthesized a class of rigid-featured chiral tridentate Phenol-2NO ligands,that incorporate the advantages of both the phenol skeleton and pyrroloimidazolone-based N-oxide moiety,from readily available L-prolinamides in operationally simple two steps and up to 44%overall yield.More importantly,using an achiral quinoline derivative as an additive,the newly developed Phenol-2NO ligand could serve as the anioic ligand upon deprotonative activation to coordinate to Zn(II)to form a highly enantioselective catalyst for the asymmetric Michael-type Friedel-Crafts alkylation reaction of indoles with 2,3-dioxopyrrolidines.Excellent yields(up to 90%)and high enantioselectivities(up to 99%ee)are obtained for a wide range of substrates under mild conditions.Experiments and DFT calculations revealed the reaction mechanism and the origins of the enantioselectivity.This also represented the first activation of phenol-type ligand/metal complex by an achiral organic base as the additive in asymmetric catalysis.

Construction of Acyclic Quaternary Carbon Stereocenters via Enantioselective Nickel Catalysis

The construction of acyclic quaternary carbon stereocenters,which are ubiquitous in many bioactive compounds,pharmaceuticals and natural products,has been a long persuit in synthetic organic chemistry.Among numerous methods,enantioselective nickel-catalysis has attracted incremental attention in recent years.This review summarizes the recent development in the asymmetric strategies,research progress,mechanistic investigations for the generation of acyclic quaternary carbon stereocenters via enantioselective nickel catalysis.

One stone three birds:Ni-catalyzed asymmetric allenylic substitution of allenic ethers,hydroalkylation of 1,3-enynes and double alkylation of enynyl ethers

The development of low-cost,earth-abundant and environmentally benign transition metal catalysts,which can catalyze multiple different types of asymmetric reactions,is an important objective in mod-ern asymmetric catalysis.Herein we demonstrate that a chiral Ni/P-Phos catalyst achieves three types of asymmetric reactions:allenylic substitution of racemic allenic ethers,1,4-hydroalkylation of prochiral 1,3-enynes and double alkylation of newly designed enynyl ether reagents.Three methods complement each other and produce various axially chiral allene derivatives bearing a pyrazolidine-3,5-dione unit,which is widely present in drugs and biologically active molecules with versatile pharmacological activities.