Asymmetric Allylic Reaction Research Articles

Asymmetric Allylic Amination of Alkyl-Substituted Allylic Carbonates with Pyridones Catalyzed by the Krische Iridium Complex.

An efficient Ir-catalyzed asymmetric allylic amination reaction of alkyl-substituted allylic carbonates is disclosed. With the Krische iridium complex as the catalyst, asymmetric allylic amination of alkyl-substituted allylic carbonates with pyridones proceeds effectively, affording pyridone derivatives containing a stereocenter α to the nitrogen atom in excellent yields and enantioselectivity (up to 99% yield, 95% ee). This catalytic system broadens the substrate scope of the reaction compared with that of the known catalytic systems. This reaction can also be conducted on a gram scale, further enhancing its potential for synthetic application.

Enantioselective nickel-catalyzed anodic oxidative dienylation and allylation reactions

Precision control of stereochemistry in radical reactions remains a formidable challenge due to the prevalence of incidental racemic background reactions resulting from undirected substrate oxidation in the absence of chiral induction. In this study, we devised an thoughtful approach—electricity-driven asymmetric Lewis acid catalysis—to circumvent this impediment. This methodology facilitates both asymmetric dienylation and allylation reactions, resulting in the formation of all-carbon quaternary stereocenters and demonstrating significant potential in the modular synthesis of functional and chiral benzoxazole-oxazoline (Boox) ligands. Notably, the involvement of chiral Lewis acids in both the electrochemical activation and stereoselectivity-defining radical stages offers innovative departures for designing single electron transfer-based reactions, significantly underscoring the relevance of this approach as a multifaceted and universally applicable strategy for various fields of study, including electrosynthesis, organic chemistry, and drug discovery.

Asymmetric three-component Tsuji-Trost allylation reaction enabled by chiral aldehyde/palladium combined catalysis.

Despite the long-standing exploration of the catalytic asymmetric Tsuji-Trost allylation reaction since the mid-20th century, most reported instances have adhered to a two-component approach. Here, we present a remarkably efficient three-component asymmetric allylation reaction enabled by the collaborative action of chiral aldehyde and palladium. A diverse array of NH2-unprotected amino acid esters, aryl or alkenyl iodides, and allyl alcohol esters exhibit robust participation in this reaction, resulting in the synthesis of structurally diverse non-proteinogenic α-amino acid esters with favorable experimental outcomes. Mechanistic investigations reveal the dominance of the allylation/Heck coupling cascade in reactions involving electron-rich aryl iodides, while the Heck coupling/allylation cascade emerges as the dominant pathway in reactions involving electron-deficient aryl iodides. This chiral aldehyde/palladium combining catalytic system precisely governs the chemoselectivity of C-allylation and N-allylation, the regioselectivity of linear and branched allylation, and the enantioselectivity of C-allylation products.

Palladium-catalyzed enantioselective umpolung allylation of amido-tethered allylic carbonates with isatin-derived ketimines.

A palladium-catalyzed enantioselective umpolung allylation reaction of amido-tethered allyl carbonates with N-2,2,2-trifluoroethylisatin ketimines has been realized herein. The reaction worked well under mild reaction conditions to give various chiral oxindole derivatives in moderate to excellent yields with high enantioselectivities. Notably, this work represents the first Pd-catalyzed asymmetric umpolung allylation reaction of N-2,2,2-trifluoroethylisatin ketimines.

TADDOL-based P,S-bidentate diastereomeric ligands in asymmetric allylation and hydrogenation reactions

Diastereomeric P,S-bidentate phosphoramidite ligands with TADDOL core and (1R,2S)-1,2-diphenyl-2-(phenylthio)-ethan-1-amine residue were synthesized. These ligands provided up to 76% ee in the Pd-catalyzed alkylation of (E)-1,3-diphenylallyl acetate with dimethyl malonate, up to 70% ee in the amination of this substrate with pyrrolidine, and 89–95% ee in the Rh-catalyzed asymmetric hydro- genation of dimethyl itaconate and methyl (Z)-2-acetamido-3-arylacrylates. The different contributions of diastereomeric chiral inducers to the catalytic outcome are discussed.

Pd-Catalyzed intermolecular asymmetric allylic dearomatization of 1-nitro-2-naphthols with MBH adducts.

An asymmetric allylic dearomatization reaction of 1-nitro-2-naphthol derivatives with Morita-Baylis-Hillman (MBH) adducts has been developed. By utilizing Pd catalyst derived from Pd(OAc)2 and Trost ligand (R,R)-L1, the reaction proceeded smoothly in 1,4-dioxane at room temperature, affording substituted β-naphthalenones in good yields (up to 92%) and enantioselectivity (up to 90% ee). A range of substituted 1-nitro-2-naphthols and MBH adducts were found to be compatible under the optimized conditions. This reaction provides a convenient method for the synthesis of enantioenriched 1-nitro-β-naphthalenone derivatives.

Palladium-Catalyzed Directed Atroposelective C-H Iodination to Synthesize Axial Chiral Biaryl N-Oxides via Enantioselective Desymmetrization Strategy.

The discovery of enantioselective desymmetrization reactions to provide practical synthesis of enantio-enriched atropisomeric biaryls is a challenging topic in the field of asymmetric catalysis. Herein, we report a highly enantioselective desymmetrization reaction for the synthesis of axially chiral biaryl N-oxides by atroposelective C-H iodination by using Pd(II) coordinated by N-benzoyl-l-phenylalanine as a chiral catalyst at room temperature. A broad range of products were obtained in high yields (up to 99 %) with excellent enantioselectivities (up to 98 % ee). The products could be synthesized in gram scale, one of which was proved to be a powerful organocatalyst in asymmetric allylation reaction. Mechanistic evidence as well as DFT calculations point towards the factors that lead to high reactivity and excellent enantiocontrol in this reaction.

Chiral Bismuth-Rhodium Paddlewheel Complexes Empowered by London Dispersion: The C-H Functionalization Nexus.

Heterobimetallic [BiRh] tetracarboxylate catalysts endowed with 1,3-disilylated phenylglycine paddlewheels benefit from interligand London dispersion. They were originally designed for asymmetric cyclopropanation but are now shown to perform very well in asymmetric C-H functionalization reactions too. Because of the confined ligand sphere about the derived donor/acceptor carbenes, insertions into unhindered methyl groups are kinetically favored, although methylene units also react with excellent levels of asymmetric induction; even gaseous ethane is a suitable substrate. Moreover, many functional groups in both partners are tolerated. The resulting products are synthetically equivalent to the outcome of traditional asymmetric ester alkylation, allylation, benzylation, propargylation and aldol reactions and therefore constitute a valuable nexus to more conventional chemical logic.

Chiral Bismuth‐Rhodium Paddlewheel Complexes Empowered by London Dispersion: The C−H Functionalization Nexus

AbstractHeterobimetallic [BiRh] tetracarboxylate catalysts endowed with 1,3‐disilylated phenylglycine paddlewheels benefit from interligand London dispersion. They were originally designed for asymmetric cyclopropanation but are now shown to perform very well in asymmetric C−H functionalization reactions too. Because of the confined ligand sphere about the derived donor/acceptor carbenes, insertions into unhindered methyl groups are kinetically favored, although methylene units also react with excellent levels of asymmetric induction; even gaseous ethane is a suitable substrate. Moreover, many functional groups in both partners are tolerated. The resulting products are synthetically equivalent to the outcome of traditional asymmetric ester alkylation, allylation, benzylation, propargylation and aldol reactions and therefore constitute a valuable nexus to more conventional chemical logic.

Recent Advances in the Total Synthesis of Aspidosperma and Kopsia Alkaloids Using Tetracyclic Pyridocarbazoles as Versatile Building Blocks

AbstractOver the past decades, aspidosperma and kopsia alkaloids have attracted significant interest by the organic synthetic community owing to their intricate fused‐ring structures and broad biological activities. Consequently, numerous strategically distinct total syntheses have been accomplished, among which tetracyclic pyridocarbazoles have seen widespread adoption as versatile building blocks. In this review, we elaborate and discuss the synthesis of such tetracyclic pyridocarbazoles according to the different approaches for the establishment of the all‐carbon quaternary center at C5. This includes (1) classic synthetic reactions (cycloaddition, Michael addition, nucleophilic substitution, and Claisen rearrangement), (2) palladium‐catalyzed asymmetric decarboxylative allylation reactions, and (3) thiourea‐catalyzed asymmetric Michael addition reactions. Furthermore, we also describe the late‐stage key transformations in the realm of the total syntheses of aspidosperma and kopsia alkaloids.magnified image

Imbuing an Old Heterocycle with the Power of Modern Catalysis: An Isoxazolidin-5-one Story.

Isoxazolidin-5-ones have been regarded as β-amino acid surrogates owing to their labile N-O bond. While many efforts have been devoted to the catalytic enantioselective synthesis of the core of this heterocycle, its further transformation has been less explored, especially in the context of catalysis. This review summarizes the author's research on the development of catalytic reactions using isoxazolidin-5-ones as substrates. Asymmetric catalysis has proven effective for C-C bond formation at the carbonyl α-carbon. Catalytic asymmetric allylation and direct Mannich-type reactions have been developed. Further, the resulting products have been readily converted into the corresponding quaternary β2,2-amino acids. Moreover, isoxazolidin-5-ones have been identified as alkyl nitrene precursors in the presence of a suitable metal catalyst. The generated metallonitrene undergoes either the electrophilic amination of the aromatic ring or aliphatic C-H insertion, affording a series of cyclic β-amino acids. A remarkable difference in chemoselectivity between rhodium and copper alkyl nitrenes has also been demonstrated, highlighting the unique nature of the underexplored reactive intermediates. The various linear and cyclic β-amino acids obtained through the study are likely to find great utility in a broad range of chemical sciences.

Correction to “Kinetic Resolution of 2H-Azirines by Asymmetric Allylation Reactions”

Correction to “Kinetic Resolution of <i>2H</i>-Azirines by Asymmetric Allylation Reactions”

Kinetic Resolution of 2H-Azirines by Asymmetric Allylation Reactions

Kinetic Resolution of 2<i>H</i>-Azirines by Asymmetric Allylation Reactions

Ruthenium-Catalyzed Asymmetric Dehydrative Allylic Cyclization of Five-Membered Chalcogen Heteroaromatics

AbstractThe asymmetric dehydrative intramolecular allylation reactions of furan and thiophene were performed using a cationic cyclopentadienyl-ruthenium (CpRu) complex of a chiral pyridine carboxylic acid, namely Cl-Naph-PyCOOH. Both furan and thiophene tethered with an allylic alcohol gave the corresponding bicyclic compounds in high yields and enantioselectivities using 0.1–5 mol% of the catalyst. The reaction was found to proceed via a similar enantioface selection mechanism to that previously reported by our group, which involved halogen and hydrogen bond formation, in addition to the generation of an intermediate σ-allyl complex.

Mechanistic Origins of Stereodivergence in Asymmetric Cascade Allylation and Cyclization Reactions Enabled by Synergistic Cu/Ir Catalysis

Mechanistic Origins of Stereodivergence in Asymmetric Cascade Allylation and Cyclization Reactions Enabled by Synergistic Cu/Ir Catalysis

Enantioselective Synthesis of 3-Allylindolizines via Sequential Rh-Catalyzed Asymmetric Allylation and Tschitschibabin Reaction.

The first highly regio- and enantioselective synthesis of 3-allylindolizines has been developed by the sequential Rh-catalyzed asymmetric allylation and Tschitschibabin reaction. Above the 20:1 branch/linear ratio, up to a 96% yield and 99% ee could be obtained with the help of tert-butyl-substituted chiral bisoxazolinephosphine ligand. In situ generated highly nucleophilic 2-alkylpyridinium ylides are utilized to undergo the asymmetric alkylation reaction before cyclization.

Recent Advances in Synthesis of Chiral Thioethers.

Chiral thioethers is an important class of organosulfur molecules with extensive applications, especially in the field of medicine and organic synthesis. This review discusses the recent progress of synthesis of enantioenriched chiral thioethers and hopes to be helpful for related research in the future. It is summarized from organosulfur compounds-participating organic reaction types, including nucleophilic substitution, cross coupling, sulfa-Michael addition, sulfenylation, asymmetric allylic reaction, asymmetric Doyle-Kirmse reaction, Pummerer-type rearrangement, Smiles rearrangement,[2,3] Stevens and Sommelet-Hauser rearrangement.

π-Coordinating Chiral Primary Amine/Palladium Synergistic Catalysis for Asymmetric Allylic Alkylation.

We report an arene-containing chiral primary amine as a dual aminocatalyst and ligand: the π-coordinating aminocatalyst/palladium synergistic catalysis for asymmetric allylic alkylation of α-branched β-ketocarbonyls. The use of arene-containing chiral primary amine catalyst led to not only enhanced reaction rate but also reversed chiral induction compared with its sterically bulky derivative. Both enantiomers of the allylic adducts bearing acyclic all-carbon quaternary stereocenters could be obtained from the same configured chiral aminocatalysts with high efficiency and excellent regio-, stereo-, and enantioselectivity. Mechanistic studies revealed a distinctive Pd-arene π-coordination mode for effective catalysis. The π-coordinating chiral primary amine catalyst could be successfully applied in the asymmetric allylation reactions of vinylethylene carbonates, vinyl epoxides, or simple allylic alcohols.

Access to P-chiral sec- and tert-phosphine oxides enabled by Le-Phos-catalyzed asymmetric kinetic resolution.

The synthesis of P-stereogenic building blocks is extremely difficult. Herein we report an efficient kinetic resolution of secondary phosphine oxides via a Le-Phos-catalyzed asymmetric allylation reaction with Morita–Baylis–Hillman carbonates. This method provides facile access to enantioenriched secondary and tertiary P-chiral phosphine oxides with broad substrate scope, both of which could serve as P-stereogenic synthons, and can be rapidly incorporated into a given scaffold bearing a P-stereocenter. The highly desirable late stage modifications demonstrate the practicability of our method and can be a critical contribution to obtaining optimal P-chiral catalysts and ligands.

Bi(OAc)3/chiral phosphoric acid catalyzed enantioselective allylation of seven-membered cyclic imines, dibenzo[b,f][1,4]oxazepines.

An efficient asymmetric allylation reaction of allylboronates with seven-membered cyclic imines, dibenzo[b,f][1,4]oxazepines, is described. The reaction, which is catalyzed by a Bi(OAc)3/CPA system, gives a range of chiral nitrogen-containing heterocycle structures in high yields and with good enantioselectivities. The conversion of these products to nitrogen-containing heterocycles is also demonstrated.