Display omitted The goal of this review is to collect the major developments in organocatalytic dynamic kinetic resolution reported since the beginning of 2011, well illustrating that the synthetic ...scope of these powerful processes allowing the resolution of racemic compounds with up to 100% yield has been widely expanded in the last five years. Indeed, an important number of chiral organocatalysts are now available that afford excellent levels of stereocontrol in a myriad of transformations evolving through dynamic kinetic resolution that could only previously be achieved by using biocatalysts. This review is divided into six sections, according to the different types of organocatalytic activation modes employed in these reactions, such as aminocatalysis, N-heterocyclic carbene catalysis, hydrogen-bonding catalysis, Brønsted acid catalysis, Brønsted base catalysis, and Lewis base catalysis.
Combining the advantages of homogeneous and heterogeneous catalysis is highly desired but remains a challenging goal. Herein, we fabricated a semiheterogeneous metal–enzyme-integrated catalyst using ...soluble porous imine molecule cages (IMCs), which could partially dissolve in organic solvents under heating conditions for catalytic tasks while precipitate completely at room temperature for catalyst recovery. The IMCs play three vital roles: (1) acting as a support and stabilizer for metal nanoparticles and enzymes, (2) partially solubilizing the heterogeneous catalyst in organic medium, and (3) creating hydrophobic and basic microenvironments for improved catalytic efficiency. The covalent immobilization of the enzyme by utilizing imine bonds via the Ugi-type reaction was disclosed, in which the effect of different parameters on enzyme immobilization and the structure–activity relationship were investigated. The semiheterogeneous catalyst exhibited high activity, selectivity, and reusability in chemoenzymatic dynamic kinetic resolution of amines at low temperature (50–60 °C) with high yields and enantioselectivities (up to 94% yield and 98% ee).
Chiral β‐hydroxysulfides are an important class of organic compounds which find broad application in organic and pharmaceutical chemistry. Herein we describe the development of novel biocatalytic and ...chemoenzymatic methods for the enantioselective synthesis of β‐hydroxysulfides by exploiting ketoreductase (KRED) enzymes. Four KREDs were discovered from a pool of 384 enzymes identified and isolated through a metagenomic approach. KRED311 and KRED349 catalysed the synthesis of β‐hydroxysulfides bearing a stereocentre at the C−O bond with opposite absolute configurations and excellent ee values by novel chemoenzymatic and biocatalytic‐chemical‐biocatalytic (bio‐chem‐bio) cascades starting from commercially available thiophenols/thiols and α‐haloketones/alcohols. KRED253 and KRED384 catalysed the enantioselective synthesis of β‐hydroxysulfides bearing a stereocentre at the C−S bond with opposite enantioselectivities by dynamic kinetic resolution (DKR) of racemic α‐thioaldehydes.
Four ketoreductases (KREDs) were identified for the enantioselective synthesis of β‐hydroxysulfides. KRED311 and KRED349 catalyse the synthesis of β‐hydroxysulfides bearing a stereocentre at the C−O bond with opposite absolute configurations via chemoenzymatic cascades from thiophenols/thiols and α‐haloketones/alcohols. KRED253 and KRED384 catalyse the synthesis of β‐hydroxysulfides bearing a stereocentre at the C−S bond with opposite enantioselectivities by dynamic kinetic resolution (DKR) of racemic α‐thioaldehydes.
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•Recent advances in lipases and their use in combination with metal catalyst to access chiral intermediates in last decade.•Development of transition metal based racemization ...catalysts for utilization in DKR protocols.•Timelines and breakthroughs in the development of transition metal based racemization catalysts.•Widening of the range of chiral alcohols and amines that are employed as substrates in lipase catalyzed KR.•Applications of lipase and metal combination to access other chiral intermediates.
The importance of chiral organic intermediates in various industrial sectors cannot be underestimated. Lipases and their use in combination with metal catalysts is a promising and facile approach to obtain enantiomerically pure chiral intermediates like alcohols and amines. The area of lipase-mediated kinetic resolution (KR) and its dynamic counterpart (dynamic kinetic resolution, DKR) employing lipases and metal based racemization catalysts has shown extensive and stimulating advances in the recent years. The present review highlights the recent progress in this field pertaining to the development of transition metal based racemization catalysts for utilization in DKR protocols and also widening of the application for a range of chiral alcohols and amines that are employed as substrates in lipase catalyzed KR. In addition, the developments in the lipase catalyzed protocols to access other chiral intermediates such as esters, amides, aminoacids etc and their derivatives are also discussed.
Diaryl ethers are widespread in biologically active compounds, ligands and catalysts. It is known that the diaryl ether skeleton may exhibit atropisomerism when both aryl rings are unsymmetrically ...substituted with bulky groups. Despite recent advances, only very few catalytic asymmetric methods have been developed to construct such axially chiral compounds. We describe herein a dynamic kinetic resolution approach to axially chiral diaryl ethers via a Brønsted acid catalyzed atroposelective transfer hydrogenation (ATH) reaction of dicarbaldehydes with anilines. The desired diaryl ethers could be obtained in moderate to good chemical yields (up to 79 %) and high enantioselectivities (up to 95 % ee) under standard reaction conditions. Such structural motifs are interesting precursors for further transformations and may have potential applications in the synthesis of chiral ligands or catalysts.
A dynamic kinetic resolution approach was developed for the synthesis of axially chiral diaryl ethers via a Brønsted acid catalyzed atroposelective transfer hydrogenation (ATH) reaction of dicarbaldehydes with anilines. The chiral phosphoric acid catalyzed dynamic kinetic resolution strategy has provided a modular platform for the synthesis of axially chiral diaryl ethers.
The Cover Feature illustrates the high reactive catalytic system for the Asymmetric Transfer Hydrogenation‐Dynamic Kinetic Resolution (ATH‐DKR) of isoflavones obtained by the entanglement of ...Noyori‐Ikariya Ru(II) complexes and sodium formate as the hydrogen source. The central couple in the image are served an isoflavone in a tray representing how mild and neutral conditions allow the ATH‐DKR reaction of several isoflavones with different substituents in the 2'‐position to proceed. The outside panel shows the general reaction diagram by which ten cis‐3‐phenylchroman‐4‐ols (>20:1 dr) in good yields (up to 86%) and excellent enantioselectivities (up to >99:1 er) were obtained. The framed structures (inside) represent the synthetic applications of these chiral compounds. In their Full Paper, F. V. Gaspar et al. obtained enantioenriched isoflavanones under mild metal‐free oxidation of the cis‐3‐ phenylchroman‐4‐ols while pterocarpans were synthesized by two strategies: an acid‐catalyzed cyclization and a novel approach based on a Pd‐catalyzed C‐O intramolecular cross‐coupling reaction. More information can be found in the Full Paper by F. V. Gaspar et al.
Biaryl compounds with axial chirality are very common in synthetic chemistry, especially in catalysis. Axially chiral biaryls are important due to their biological activities and extensive ...applications in asymmetric catalysis. Thus the development of efficient enantioselective methods for their synthesis has attracted considerable attention. This Minireview discusses the progress made in catalytic kinetic resolution of biaryl compounds and chronicles significant advances made recently in catalytic kinetic resolution of biaryl scaffolds.
Roll out the biaryls: Axially chiral biaryls are very attractive due to their wide applications in asymmetric catalysis. The development of efficient enantioselective syntheses of chiral biaryls has attracted considerable attention. This Minireview highlights recent progress achieved in the field of catalytic kinetic resolution of biaryl compounds.
An efficient dynamic kinetic resolution (DKR) approach for the synthesis of axially chiral diamines has been developed on the basis of a ruthenium-catalyzed enantioselective transfer hydrogenation. ...The strategy relies on the configurational instability of cyclic biaryl aminal precursors in equilibrium with their amino-imine open forms, as supported by DFT calculations. This protocol features a broad substrate scope of aliphatic amines and biaryl scaffolds and proceeds under very mild conditions, allowing the preparation of BINAM homologues in good to high yields and nearly perfect enantioselectivities (up to 99% ee).
Catalytic asymmetric dynamic kinetic resolution of configurationally labile bridged biaryls is emerging as a powerful strategy for atropisomer synthesis. However, the reported examples suffer from an ...inherent challenge as the reactivity is highly dependent on the torsional strain of the biaryl substrates, which significantly narrows down the scope and hampers the application. Herein, we report our discovery and development of a torsional strain‐independent reaction between biaryl thionolactones and activated isocyanides. By employing auto‐tandem silver catalysis, a universal synthesis of both tri‐ and tetra‐ortho‐substituted thiazole‐containing biaryls was realized in high yields with high enantioselectivities. In addition, these products could be facilely converted to a novel type of bridged biaryls bearing an eight‐membered lactone. Mechanistic studies were carried out to elucidate the cause of this unusual torsional strain‐independent reactivity.
A torsional strain‐independent reaction between biaryl thionolactones and activated isocyanides is reported. Under auto‐tandem silver catalysis, both tri‐ and tetra‐ortho‐substituted biaryls were obtained in high yields and enantioselectivities. These products could be converted to bridged biaryls bearing an eight‐membered lactone. Mechanistic studies provided key insights into the cause of this unusual torsional strain‐independent reactivity.
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