Catalytic Enantioselective Reaction Research Articles

Asymmetric Mannich/Radical Debromination Cascade of α‐Bromoketones by Dipeptide‐Phosphonium Salt Catalysis: Enantioselective Synthesis of β‐Amino Ketone‐Pyrazolinones

AbstractWe herein demonstrated an organocatalytic asymmetric Mannich/radical debromination cascade of α‐brominated ketones. With this protocol, a diversity of chiral β‐amino ketone‐pyrazolinone scaffolds, which have important versatilities in medicine and chemical synthesis, were constructed in high yields (up to 94%) with excellent enantioselectivities (up to 99% ee). This methodology features mild reaction conditions, broad substrate scope, and high functional group tolerance. Moreover, mechanistic investigations revealed that this cascade reaction proceeds through a bifunctional phosphonium salt‐catalyzed Mannich reaction of α‐brominated ketones with pyrazolinone ketimines, which is followed by an oxygen‐induced radical debromination. This protocol represents a novel activation mode for α‐brominated ketones and opens new avenues for catalytic enantioselective radical reactions under ion‐pair system.

Direct Catalytic Enantioselective Reaction of α-Isocyanoacetonitriles with Ketimines Using Cinchona Alkaloid Amide-Cu(II) Catalysts.

The first enantioselective reaction of α-isocyanoacetonitriles was developed. The reaction of various α-isocyanoacetonitriles with ketimines using cinchona alkaloid amide-Cu(II) catalysts afforded imidazolines with consecutive tetrasubstituted stereogenic carbon centers in good yields and high diastereo- and enantioselectivities. The stereoselectivity of the reaction is explained on the basis of the control experiment and density functional theory (DFT) calculations. The products were subsequently converted into chiral compounds. This process highlights the possible use of α-isocyanoacetonitriles for asymmetric and organic syntheses.

Enantioselective direct Michael addition of cyanohydrin ether derivatives to enones catalyzed by chiral bis(guanidino)iminophosphorane organosuperbase.

The direct use of cyanohydrin ether derivatives as less acidic pronucleophiles was achieved for the first time in the catalytic enantioselective Michael addition reaction under transition metal free conditions. Chiral bis(guanidino)iminophosphoranes as the higher order organosuperbase facilitated the intended catalytic Michael addition to enones, giving rise to the corresponding products in high yields with moderate to high diastereo- and enantioselectivities in most cases. Further elaboration of the corresponding enantioenriched product was conducted by derivatization into a lactam derivative through hydrolysis followed by cyclo-condensation.

Accessing unnatural α-amino acids with tetrasubstituted stereogenic centers via catalytic enantioselective reactions of ketimine-type α-iminoesters/α-iminoamides.

Catalytic enantioselective synthesis methodologies have been actively explored and developed owing to the significance of chiral molecules and their utilities. In particular, unnatural α-amino acids with tetrasubstituted stereogenic carbon centers (α-tertiary amino acids; ATAAs) are undoubtedly among the most valuable compounds. Asymmetric addition to an α-iminoester or α-iminoamide is widely recognized as a straightforward, powerful, and atom-economical strategy for accessing optically active α-amino acids and their derivatives. However, this type of chemistry, which relies on ketimine-type electrophiles, was quite limited only a few decades ago owing to low reactivities and difficulties associated with enantiofacial control. This feature article comprehensively overviews this research field and highlights the significant progress that has been made. In particular, it focuses on the chiral catalyst system and the transition state as the key parameters for such reactions.

Catalytic asymmetric C-H insertion reactions of vinyl carbocations.

From the preparation of pharmaceuticals to enzymatic construction of natural products, carbocations are central to molecular synthesis. Although these reactive intermediates are engaged in stereoselective processes in nature, exerting enantiocontrol over carbocations with synthetic catalysts remains challenging. Many resonance-stabilized tricoordinated carbocations, such as iminium and oxocarbenium ions, have been applied in catalytic enantioselective reactions. However, their dicoordinated counterparts (aryl and vinyl carbocations) have not, despite their emerging utility in chemical synthesis. We report the discovery of a highly enantioselective vinyl carbocation carbon-hydrogen (C-H) insertion reaction enabled by imidodiphosphorimidate organocatalysts. Active site confinement featured in this catalyst class not only enables effective enantiocontrol but also expands the scope of vinyl cation C-H insertion chemistry, which broadens the utility of this transition metal-free C(sp3)-H functionalization platform.

Organocatalytic Enantioselective Diels-Alder Reaction of 2-Trifluoroacetamido-1,3-dienes with α,β-Unsaturated Ketones.

We report herein the first examples of chiral phosphoric acid-catalyzed enantioselective Diels-Alder reactions between 2-trifluoroacetamido-1,3-dienes 1 and α,β-unsaturated carbonyl compounds 2. Polysubstituted 1-acetamido cyclohexenes 3 were formed in high yields with excellent diastereo- and enantioselectivities. The reaction proceeds through a stepwise process as shown by deuterium labelling experiments. A catalytic enantioselective three-component reaction of 1, 2 and ortho-hydroxybenzhydryl alcohols 4 was subsequently developed furnishing the densely functionalized hexahydroxanthenes 5 in a highly stereoselective manner. This multicomponent reaction generates four chemical bonds with concurrent creation of five contiguous stereocenters.

Chiral Crown Ethers Accessed from Catalytic Enantioselective Desymmetrization Reactions.

A diversity of unprecedented chiral aza-crown ethers were synthesized straightforwardly from readily available and inexpensive aza-crown ethers. Catalyzed by a chiral phosphoric acid, desymmetrization of an array of symmetric N-arylated aza-crown ethers through tert-amino reaction proceeded efficiently under mild conditions to produce novel tetrahydroquinoline-fused aza-crown ethers in good to excellent yields with up to 96% ee. Our strategy opens a new route to functionalized chiral crown ethers.

Recent Advances in Enantioselective Organocatalytic Reactions Enabled by N-Heterocyclic Carbenes (NHCs) Containing Triazolium Motifs

AbstractN-Heterocyclic carbenes (NHCs) containing triazolium motifs have emerged as a powerful tool in organocatalysis. Recently, various NHC-catalyst-mediated organic transformations have been developed. This review aims to compile the current state of knowledge on enantioselective NHC-triazolium-catalyzed named reactions as well as introduce newly developed catalytic methods. Furthermore, this review article framework provides an excellent opportunity to highlight some of the unique applications of these catalytic procedures in the synthesis of natural products and biologically active compounds, notably the extensive processes for the preparation of substituted chiral alcohols and their derivatives. This review also provides an overview of the synthesis of chiral NHC-triazolium-catalyst libraries and their applications in catalytic enantioselective reactions.1 Introduction2 Synthesis of N‑Heterocyclic Carbenes Containing Triazolium Motifs2.1 Pyrrolidine-Based Triazoliums NHCs: Px 2.2 Morpholine-Based Triazoliums NHCs: Mx 2.3 Aminoindane-Based Triazoliums NHCs: AMx 2.4 Oxazolidine-Based Heteroazoliums NHCs: Ox 2.5. Acyclic Triazoliums NHCs: Ax 3 Enantioselective Organocatalytic Reactions3.1 Enantioselective Benzoin Reactions3.1.1 Aldehyde–Aldehyde Homo-Benzoin Reactions3.1.2 Aldehyde–Aldehyde Cross-Benzoin Reactions3.1.3 Aldehyde–Ketone Cross-Benzoin Reactions3.1.4 Aldehyde–Imine Cross-Benzoin Reactions3.1.5 Aza-Benzoin Reactions3.2 Enantioselective Stetter Reactions3.2.1 Intramolecular Stetter Reactions3.2.2 Intermolecular Stetter Reactions3.3 Enantioselective Diels–Alder Reactions3.4 Enantioselective Michael Additions3.5 Enantioselective Rauhut–Currier Reactions3.6 Enantioselective Cycloadditions3.7 Enantioselective Michael–Stetter Cascade Reactions3.8 Enantioselective Annulation Reactions3.9 Synthesis of Spiro Compounds3.10 Heterocycle Synthesis3.11 Carbocycle Synthesis3.12 Asymmetric Steglich Rearrangement Reactions3.13 NHC-Mediated Asymmetric Acylation/Hydroacylation Reactions3.14 Enantioselective α-Fluorination of Aliphatic Aldehydes3.15 Functionalization of Carboxylic Anhydrides by NHC Catalysis3.16 Asymmetric β-Boration of Acyclic Enones3.17 Synthesis of Tropane Derivatives via Organocatalysis3.18 Dynamic Kinetic Resolution of Pyranones via NHC Catalysis3.19 Enantioselective Umpolung Reactions3.20 Enantioselective Esterification of Ketenes3.21 Asymmetric Synthesis of trans-γ-Lactams3.22 Oxy-Cope Rearrangements3.23 Claisen Rearrangements3.24 Enantioselective Synthesis of Complex Heterocycles3.25 Atroposelective Synthesis of N-Aryl Succinimides3.26 Asymmetric α-Fluorination via Cascade Reactions4 Conclusion

Cooperative Pd/Cu-catalyzed diastereodivergent coupling of allenamides and aldimine esters to access the Mannich-type motifs

Mannich reaction is a significant transformation to prepare chiral amines from imine; however, vinylimines are still unaddressed substrates in this transformation due to the inherent competition between the Mannich and Michael addition. Herein we report a cooperative Pd/Cu-catalyzed enantioselective coupling of allenamides with aldimine esters for expeditious access to Mannich-type motifs α,β-diamino esters. The reaction has excellent regioselectivity, and by selecting the combinations of Pd and Cu catalysts with appropriate chiralities, both the syn- and anti- coupling products could be selectively prepared with high enantio-, diastereoselectivities. This work represents a rare example of employing cooperative catalysis for achieving diastereodivergent Mannich-type coupling reaction and would inspire further studies in this field. • Formal Mannich reaction of vinylimines • Cooperative palladium/copper catalysis-enabled stereodivergent coupling • Access all four stereoisomers of α,β-diamino esters Mannich reaction is among the most useful methods in preparing chiral amine compounds. Despite the huge success in catalytic enantioselective Mannich reaction, diastereodivergent preparing both syn- and anti- Mannich products from the same set of substrates is still underdeveloped. On the other hand, due to the inherent regioselectivity issue (Mannich versus Michael addition), vinylimines are still less-solved challenging substrates in Mannich reaction. We report a cooperative Pd/Cu-catalyzed enantioselective coupling of allenamides with aldimine esters for access to Mannich-type motifs α,β-diamino esters. By choosing the appropriate combination of chiralities of Pd and Cu catalysts, diastereodivergent access to both the syn - and anti -coupling products could be achieved with good regio-, diastereo-, and enantioselectivities. This work sheds light on using cooperative catalysis to achieve Mannich-type motifs in a diastereodivergent manner. Zi et al. describe a cooperative Pd/Cu catalyst system for diastereodivergent coupling of allenamides with aldimine esters, which provides a formal Mannich-type reaction of vinylimines. By choosing the appropriate combination of chiralities of Pd and Cu catalysts, all four stereoisomers of α,β-diamino esters could be selectively achieved with high enantio- and diastereoselectivities.

Aromatic π-Components for Enantioselective Heck Reactions and Heck/Anion-Capture Domino Sequences.

Olefin functionalization represents one of the most important synthetic transformations in organic synthesis. Over the past decades, palladium-catalyzed enantioselective Heck reactions, and Heck/anion-capture domino sequences through olefin carbopalladation followed by termination of the resulting alkyl-Pd species have been extensively developed. Extension of the coupling partners from classical olefins to other π-components would enable further advances and open new space in this field. Aromatics are important and easily available bulk chemicals. Dearomative transformation of endocyclic aromatic π-bonds via the Heck reaction pathway provides an efficient and straightforward route to structurally diverse alicyclic compounds. Nevertheless, major challenges for this transformation include aromaticity breaking and reactivity and selectivity issues.Recently, we have engaged in developing catalytic enantioselective dearomative Heck reactions and related domino reactions. A range of heteroarenes and naphthalenes have been employed as novel π-coupling partners in these reactions. Through dearomative migratory insertion of endocyclic aromatic C-C π-bonds followed by interception of the transient alkyl-Pd species, enantioselective Heck reactions, reductive Heck reactions, Heck/anion-capture difunctionalization reactions, and heteroarenyne cycloisomerization reactions have been established. Relying on β-H elimination of the alkyl-Pd intermediate, we realized enantioselective dearomative Heck reactions with a range of aromatic partners, including heterocyclic indoles, pyrroles, furans, benzofurans, and more challenging carbocyclic naphthalenes. In order to avoid the utilization of organohalide electrophiles, heteroarenyne cycloisomerization reaction was developed by merging intermolecular alkyne hydropalladation with intramolecular dearomative Heck reaction. Cycloisomerization of alkyne-tethered indoles delivered chiral indolines in excellent enantioselectivities with 100% atom economy. On the other hand, Heck/anion-capture domino sequences were established through nucleophilic trapping of the alkyl-Pd intermediate. When HCO2Na was employed as a capturing reagent, the enantioselective dearomative reductive Heck reaction of indoles was realized. By employing other nucleophiles, including alkynes, N-sulfonylhydrazones, and organoboron reagents, we developed a series of dearomative difunctionalization reactions. Two vicinal stereocenters with excellent enantio- and diastereoselectivities were constructed in the corresponding Heck/Sonogashira, Heck/vinylation, and Heck/borylation reactions. Moreover, dearomative 1,4-diarylation of naphthalenes was developed through Heck/Suzuki domino reactions, in which competitive C-H arylation and the direct Suzuki reaction were almost fully inhibited in the presence of a spiro-phosphoramidite ligand.In this Account, we provide a panoramic view of our results since 2015 on enantioselective Heck reactions and related domino sequences by extending the coupling partners from classical olefins to aromatic systems. Investigations outlined in this Account established straightforward and efficient access to a variety of structurally diverse chiral heteropolycyclic molecules starting from simple and planar aromatic compounds.

Chiral Sulfide/Phosphoric Acid Cocatalyzed Enantioselective Intermolecular Oxysulfenylation of Alkenes with Phenol and Alcohol O -Nucleophiles

Chiral Sulfide/Phosphoric Acid Cocatalyzed Enantioselective Intermolecular Oxysulfenylation of Alkenes with Phenol and Alcohol <i>O</i> -Nucleophiles

Enantioselective catalytic Povarov reactions

Catalytic asymmetric Povarov protocols have undergone an explosive growth, especially in the last ten years, since the first example was published in 1996. The use of chiral Lewis and Brønsted acids and dual strategies based on their combination with catalysts acting by hydrogen bond formation, as well as covalent aminocatalysis, are reviewed. More recent variations such as the nitroso Povarov reaction and interrupted Povarov reactions as a route to chiral scaffolds other than tetrahydroquinolines are also discussed.

Harnessing the ambiphilicity of silyl nitronates in a catalytic asymmetric approach to aliphatic \u03b23-amino acids

Nitronate anions, formally generated by α-deprotonating the corresponding nitroalkanes, are highly nucleophilic and versatile intermediates in many carbon–carbon bond-forming reactions. In contrast, the corresponding silyl nitronates are ambiphilic and react, at the same carbon atom, with both electrophiles and nucleophiles. However, while their nucleophilicity has been well exploited in catalytic enantioselective reactions with imines and aldehydes, utilizing the electrophilicity of silyl nitronates in asymmetric synthesis has remained elusive. Here we report the facile, efficient and general reactivity of readily available silyl nitronates with silyl ketene acetals, catalysed by highly Lewis-acidic and confined silylium imidodiphosphorimidate catalysts. The products of this reaction, so-called nitroso acetals, are obtained in excellent enantioselectivity and can be easily converted into N-Boc-β3-amino acid esters in a single step.

Asymmetric Aldol Reaction of Alkenyl Esters with α-Keto Esters Catalyzed by Chiral Tin Alkoxides

AbstractA catalytic enantioselective aldol reaction of alkenyl esters with α-keto esters was achieved by using an (R)-BINOL-derived chiral tin dibromide possessing 4-t-butylphenyl groups at the 3- and 3′-positions as a chiral precatalyst in the presence of sodium methoxide and methanol. Optically active aldol products possessing a chiral tertiary carbon were diastereoselectively obtained with up to 92% ee and moderate to high yields, not only from cyclic alkenyl esters, but also from acyclic ones under the influence of the chiral tin methoxide generated in situ.

A Novel Dual Organocatalyst for the Asymmetric Pinder Reaction and a Mechanistic Proposal Consistent with the Isoinversion Effect Thereof.

In general, the Pinder reaction concerns the reaction between an enolisable anhydride and an aldehyde proceeding initially through a Knoevenagel reaction followed by the ring closing process generating lactones with at least two chiral centers. These scaffolds are frequently present in natural products and synthetic bioactive molecules, hence it has attracted intense interest in organic synthesis and medicinal chemistry, particularly with respect to controlling the diastereo- and enantioselectivity. To the best of our knowledge, there has been only one attempt prior to this work towards the development of a catalytic enantioselective Pinder reaction. In our approach, we designed, synthesized, and tested dual chiral organocatalysts by combining BIMAH amines, (2-(α-(alkyl)methanamine)-1H-benzimidazoles, and a Lewis acid motif, such as squaramides, ureas and thioureas. The optimum catalyst was the derivative of isopropyl BIMAH bearing a bis(3,5-trifluoromethyl) thiourea, which afforded the Pinder products from various aromatic aldehydes with diastereomeric ratio >98:2 and enatioselectivity up to 92 ee%. Interestingly, the enantioselectivity of this catalyzed process is increased at higher concentrations and exhibits an isoinversion effect, namely an inverted "U" shaped dependency with respect to the temperature. Mechanistically, these features, point to a transition state involving an entropy-favored heterodimer interaction between a catalyst/anhydride and a catalyst/aldehyde complex when all other processes leading to this are much faster in comparison above the isoinversion temperature.

Catalytic Chemo- and Enantioselective Transformations of gem-Diborylalkanes and (Diborylmethyl)metallic Species.

Chemo- and stereoselective transformations of polyborylalkanes are powerful and efficient methods to access optically active molecules with greater complexity and diversity through programmed synthetic design. Among the various polyborylalkanes, gem-diborylalkanes have attracted much attention in organic chemistry as versatile synthetic handles. The notable advantage of gem-diborylalkanes lies in their ability to generate two key intermediates, α-borylalkyl anions and (gem-diborylalkyl) anions. These two different intermediates can be applied to various enantioselective reactions to rapidly access a diverse set of enantioenriched organoboron compounds, which can be further manipulated to generate various chiral molecule libraries via stereospecific C(sp3)-B bond transformations.In this Account, we summarize our recent contributions to the development of catalytic chemo- and stereoselective reactions using gem-diborylalkanes as versatile nucleophiles, which can be categorized as follows: (1) copper-catalyzed enantioselective coupling of gem-diborylalkanes with electrophiles and (2) the design and synthesis of (diborylmethyl)metallic species and their applications to enantioselective reactions. Since Shibata and Endo reported the Pd-catalyzed chemoselective Suzuki-Miyaura cross-coupling of gem-diborylalkanes with organohalides in 2014, Morken and Hall subsequently developed the first enantioselective analogous reactions using TADDOL-derived chiral phosphoramidite as the supporting ligand of a palladium catalyst. This discovery sparked interest in the catalytic enantioselective coupling of gem-diborylalkanes with electrophiles. Our initial studies focused on generating chiral (α-borylmethyl)copper species by enantiotopic-group-selective transmetalation of gem-diborylalkanes with chiral copper complexes and their reactions with various aldimines and ketimines to afford syn-β-aminoboronate esters with excellent enantio- and diastereoselectivity. Moreover, we developed the enantioselective allylation of gem-diborylalkanes that proceeded by reaction of in situ-generated chiral (α-borylalkyl)copper and allyl bromides. Mechanistic investigations revealed that the enantiotopic-group-selective transmetalation between gem-diborylalkanes and the chiral copper complex occurred through the open transition state rather than the closed transition state, thereby effectively generating chiral (α-borylmethyl)copper species. We also utilized (diborylmethyl)metallic species such as (diborylmethyl)silanes and (diborylmethyl)zinc halides in catalytic enantioselective reactions. We succeeded in developing the enantiotopic-group-selective cross-coupling of (diborylmethyl)silanes with aryl iodides to afford enantioenriched benzylic 1,1-silylboronate esters, which could be used for further consecutive stereospecific transformations to afford various enantioenriched molecules. In addition, we synthesized (diborylmethyl)zinc halides for the first time by the transmetalation of isolated (diborylmethyl)lithium and zinc(II) halides and their utilization to the synthesis of enantioenriched gem-diborylalkanes bearing a chiral center at the β-position via an iridium-catalyzed enantioselective allylic substitution process. In addition to our research efforts, we also include key contributions by other research groups. We hope that this Account will draw the attention of the synthetic community to gem-diboryl compounds and provide guiding principles for the future development of catalytic enantioselective reactions using gem-diboryl compounds.

Auto Tandem Catalysis: Asymmetric Vinylogous Cycloaddition/Kinetic Resolution Sequence for the Enantioselective Synthesis of Spiro‐Dihydropyranone from Benzylidene Meldrum's Acid

AbstractA catalytic enantioselective vinylogous domino reaction has been achieved from ketone‐derived benzylidene Meldrum's acid and α‐ketolactones to provide spirolactone dihydropyranones with more than 99% ee. An Auto Tandem Catalysis (ATC) process resulting from dual and complementary role of (DHQ)2PHAL organocatalyst resulted in a sequence involving an asymmetric vinylogous formal (4+2) cycloaddition of benzylidene and the subsequent kinetic resolution operating through a 1,3‐prototropic shift leading to good yields (&gt;50%) and the high selectivity.magnified image

Absolute Asymmetric Catalysis, from Concept to Experiment: A Narrative

AbstractThe generally accepted hypothesis to explain the origin of biological homochirality (that is to say, the fact that proteinogenic amino acids are left-handed, and carbohydrates right-handed, in all living beings) is to assume, in the course of prebiotic chemical evolution, the appearance of an initial enantiomeric excess in a set of chiral molecular entities by spontaneous mirror-symmetry breaking (SMSB), together with suitable amplification and replication mechanisms that overcome the thermodynamic drive to racemization. However, the achievement of SMSB in chemical reactions taking place in solution requires highly specific reaction networks showing nonlinear dynamics based on enantioselective autocatalysis, and examples of its experimental realization are very rare. On the other hand, emergence of net supramolecular chirality by SMSB in the self-assembly of achiral molecules has been seen to occur in several instances, and the chirality sign of the resulting supramolecular system can be controlled by the action of macroscopic chiral forces. These considerations led us to propose a new mechanism for the generation of net chirality in molecular systems, in which the SMSB takes place in the formation of chiral supramolecular dissipative structures from achiral monomers, leading to asymmetric imbalances in their composition that are subsequently transferred to a standard enantioselective catalytic reaction, dodging in this way the highly limiting requirement of finding suitable reactions in solution that show enantio­selective autocatalysis. We propose the name ‘absolute asymmetric catalysis’ for this approach, in which an achiral monomer is converted into a nonracemic chiral aggregate that is generated with SMSB and that is catalytically active.Our aim in this Account is to present a step-by-step narrative of the conceptual and experimental development of this hitherto unregarded, but prebiotically plausible, mechanism for the emergence of net chirality in molecular reactions.1 Introduction: The Origin of Biological Homochirality and Spontaneous Mirror-Symmetry Breaking2 Experimental Chemical Models for Spontaneous Mirror-Symmetry Breaking: The Soai Reaction and Beyond3 Spontaneous Mirror-Symmetry Breaking in Supramolecular Chemistry: Plenty of Room at the Top4 Absolute Asymmetric Catalysis: An Alternative Mechanism for the Emergence of Net Chirality in Molecular Systems 5 Experimental Realization of Top-Down Chirality Transfer to the Molecular Level6 Conclusions and Outlook

Atroposelective Construction of Axially Chiral Alkene‐Indole Scaffolds via Catalytic Enantioselective Addition Reaction of 3‐Alkynyl‐2‐indolylmethanols†

Main observation and conclusionAtroposelective construction of axially chiral alkene‐heteroaryl scaffolds is highly desired but challenging. In this work, we established an atroposelective construction of axially chiral alkene‐indole scaffolds via the strategy of catalytic enantioselective addition reaction of 3‐alkynyl‐2‐indolylmethanols with bulky nucleophiles. In this strategy, α‐amido sulfones were used as competent nucleophiles and chiral phosphoric acid (CPA) acted as suitable chiral catalyst for this addition reaction. By this strategy, a new class of axially chiral acyclic alkene‐indoles was synthesized in overall high yields (up to 86%), excellent (E/Z)‐selectivity (all &gt; 95 : 5) and good enantioselectivities (up to 92 : 8 er). This reaction represents the first catalytic enantioselective construction of axially chiral alkene‐indole frameworks, which will add a new member to the family of atropoisomeric heterocycles, especially the family of axially chiral indole compounds.

Dynamic Spin-Controlled Enantioselective Catalytic Chiral Reactions.

Enantioselective catalytic chiral reactions are important to all aspects of life sciences. Here we present the first utilization of the chiral induced spin selectivity (CISS) effect to form, enantioselectively, sp3 chiral centers in catalytic reactions, starting from achiral reagents. The enantiomeric symmetry is broken by affecting spin-controlled different reaction dynamics toward each of the enantiomers, using magnetic substrates. Two catalytic reactions are used for this purpose: a sulfide to sulfoxide oxidation and a Diels-Alder cycloaddition reaction, both catalyzed by hematite (Fe2O3). The proof of concept was evaluated by circular dichroism measurements and by chiral high-performance liquid chromatography techniques. These results provide direct evidence that the directionality of the electron spin can break enantiomeric symmetry, enabling asymmetric catalysis without using chiral reagents, solvents, or catalysts.