Enantioselective Ring Research Articles

Ligand-Controlled Regiodivergent Ring Expansion of Benzosilacyclobutenes with Alkynes en Route to Axially Chiral Silacyclohexenyl Arenes.

A ligand-controlled regiodivergent and enantioselective ring expansion of benzosilacyclobutenes with internal naphthyl alkynes has been achieved by adjusting the ligand cavity size. The ligand (S)-8H-binaphthyl phosphoramidite, featuring small methyl groups on its arms, provides a spacious cavity that favors sterically demanding Si-Csp3 ring expansion, predominantly yielding axially chiral (S)-1-silacyclohexenyl arenes. In contrast, the ligand (R)-spiro phosphoramidite, with bulky t-Bu groups on its arms, offers a compact cavity that facilitates less sterically demanding Si-Csp2 ring expansion, leading primarily to axially chiral (S)-2-silacyclohexenyl arenes. Density functional theory calculations delineate distinct mechanistic pathways for each ring expansion route and elucidate their regio- and enantioselectivity.

Application of Cyclic Diaryliodonium Salts in the Synthesis of Axially Chiral Natural Product Analogues.

The application of cyclic diaryliodonium salts in the synthesis of bioactive natural product analogues was demonstrated. Axially chiral biaryls were obtained via the enantioselective ring opening of cyclic diaryliodonium salts. Regioselective borylation was key in accessing both enantiomers of a biphenol key intermediate in eight steps overall. 8,8″-Amino biflavones were synthesized, their bioactivity profiled, and the eutomer identified. The structure-activity relationship was probed.

Substrate Directed Regio‐ and Enantioselective Ring‐Opening of Epoxides and Aziridines

AbstractThe oxirane and aziridine rings are valuable building blocks in modern synthetic chemistry and catalytic asymmetric ring opening reactions of these three membered ring systems have emerged as a powerful chemical tool for the synthesis of natural products and biologically active compounds. In this context, the regioselective ring‐opening of structurally or electronically unbiased epoxides and aziridines is challenging. Recently, metal‐catalyzed substrate directed strategies have successfully applied in the regio‐ and enantioselective ring opening of functionalized epoxy alcohols by the Yamamoto group. Subsequently, our group realized the ring opening reactions of functionalized 2,3‐aziridinyl alcohols with the dinuclear zinc complex. These enantioselective nucleophilic ring opening reactions of functionalized epoxy alcohols and aziridinyl alcohols allow for the facile synthesis of amino alcohol derivatives and the introduction of new concepts in catalysis.

Asymmetric Catalytic Ring-Expansion of 3-Methyleneazetidines with α-Diazo Pyrazoamides towards Proline-Derivatives.

We realized a highly efficient formal [1,2]-sigmatropic rearrangement of ammonium ylides generated from 3-methylene-azetidines and α-diazo pyrazoamides. The employ of readily available chiral cobalt(II) complex of chiral N,N'-dioxide enabled the ring-expansion of azetidines, affording a variety of quaternary prolineamide derivatives with excellent yield (up to 99 %) and enantioselectivity (up to 99 % ee) under mild reaction condition. For the rearrangement of ammonium ylides, the installation of a pyrazoamide group as a masked brick to build chiral scaffolds proved successful. The enantioselective ring expansion process was elucidated by DFT calculations.

Asymmetric Catalytic Ring‐Expansion of 3‐Methyleneazetidines with α‐Diazo Pyrazoamides towards Proline‐Derivatives

AbstractWe realized a highly efficient formal [1,2]‐sigmatropic rearrangement of ammonium ylides generated from 3‐methylene‐azetidines and α‐diazo pyrazoamides. The employ of readily available chiral cobalt(II) complex of chiral N,N′‐dioxide enabled the ring‐expansion of azetidines, affording a variety of quaternary prolineamide derivatives with excellent yield (up to 99 %) and enantioselectivity (up to 99 % ee) under mild reaction condition. For the rearrangement of ammonium ylides, the installation of a pyrazoamide group as a masked brick to build chiral scaffolds proved successful. The enantioselective ring expansion process was elucidated by DFT calculations.

Kinetic Resolution of trans-2,3-Aziridinyl Alcohols via Hydroxyl Directed Regio- and Enantioselective Ring Opening Reactions

An efficient kinetic resolution of racemic trans-2,3-aziridinyl alcohols is established via zinc catalyzed ring opening reactions with various amines as the nucleophiles. The directing effect of the hydroxyl group and the precise enantiodiscrimination by dinuclear zinc cooperative catalyst are the keys to success of high regioselectivity and enantioselectivity. A range of enantioenriched vicinal diamines and trans-2,3-aziridinyl alcohols were obtained in good yields with excellent ee values. To the best of our knowledge, this is the first example of directed enantioselective nucleophilic ring opening reactions of 2,3-aziridinyl alcohols.

Nickel-Catalyzed Regio- and Enantioselective Ring Opening of 3,4-Epoxy Amides and Esters with Aromatic Amines.

Herein we present a nickel-catalyzed regio- and enantioselective ring opening reaction of 3,4-epoxy amides and esters with aromatic amines as nucleophiles. This method features high regiocontrol, diastereospecific SN 2 reaction pathway, broad substrate scope, and mild reaction conditions, furnishing a wide range of γ-amino acid derivatives in a highly enantioselective manner. Notably, the selective nucleophilic attack to the C-4 position of epoxides is controlled by the directing effect of the pendant carbonyl group.

Iridium-Catalyzed Enantioselective Ring Opening of Alkenyl Oxiranes by Unactivated Carboxylic Acids.

An iridium-catalyzed enantioselective ring-opening of alkenyl oxiranes by unactivated carboxylic acids has been developed. The reaction undergoes at ambient conditions between an in-situ-generated chiral iridium-π-allyl complex and carboxylic acids to provide rapid access to valuable alkenyl diols in high yields. The synthetic utility of this method is demonstrated by the elaboration of the products into various medium and large ring-sized compounds that are part of biologically relevant molecules.

A convenient synthesis of (3S,3aR,5R,7aS,8S)-Hexahydro-4H-3,5-methanofuro[2,3-b]pyran-8-ol, a high-affinity nonpeptidyl ligand for highly potent HIV-1 protease inhibitors

We describe a practical synthesis of optically active (3S,3aR,5R,7aS,8S)-hexahydro-4H-3,5-methanofuro[2,3-b]pyran-8-ol. This stereochemically defined 6-5-5 tricyclic heterocycle is an important high-affinity P2 ligand for a variety of highly potent HIV-1 protease inhibitors that show clinical potential. The key steps involve an enantioselective ring opening of meso carbic anhydride mediated by the cinchona alkaloid. The resulting optically active acid was reduced to optically active bicyclo[2.2.1]hept-5-ene derivative which was converted to the ligand alcohol by ozonolysis, reduction, and dehydration of the resulting primary alcohol followed by ozonolytic cleavage and reduction. Optically active ligand alcohol was obtained in high enantiomeric purity (99 % ee).

Rhodium-Catalyzed Enantioselective Ring Expansion of Azetidines

Rhodium-Catalyzed Enantioselective Ring Expansion of Azetidines

Cinchona alkaloid derivative modified Fe3O4 nanoparticles for enantioselective ring opening of meso-cyclic anhydrides

Making magnetic achiral surfaces chiral for asymmetric catalysis! Enantioselective meso-cyclic anhydride ring opening is demonstrated on the surface of modified-quinidine capped Fe3O4 nanoparticles.

Access to valuable building blocks by the regio- and enantioselective ring opening of itaconic anhydride by lipase catalysis.

Herein, we report for the first time the highly regio- and enantioselective ring opening of a biobased itaconic anhydride catalyzed by the Pseudomonas cepacia lipase (PCL) in tert-butyl methyl ether (TBME) at room temperature. This method is easy, efficient and eco-friendly and can be performed in one step with a series of highly valuable monoester itaconates (achiral or enantioenriched) using various alcohols as nucleophiles with 100% atom economy. In all cases, the β-monoester isomer was the predominant product of the reaction. Using achiral primary alcohols as substrates, a variety of novel itaconates were obtained in moderate to excellent yields (50-90%). For select examples, product characterization was carried out using X-ray diffraction, in addition to the standard techniques. The application of this approach was performed for the preparation of enantioenriched 4-monoester itaconates via enzymatic kinetic resolution.

Pd(II)-Catalyzed Enantioselective Ring-Contraction for the Construction of 1,4-Benzoxazines.

Enantioselective ring-contraction reactions have not been widely reported. We have developed an enantioselective ring contraction of 5,6-dihydro-2H-benzo[b][1,4]oxazocines, affording enantiomerically enriched 3,4-dihydro-2H-1,4-benzoxazine derivatives as single regioisomers. An acidic additive is necessary in order to obtain the products with good yields and enantiomeric ratios (up to 93% yield, 98:2 er). The reaction was successfully performed on a gram scale, and the products can be derivatized easily.

Recent Developments in Z‐Selective Olefin Metathesis Reactions by Molybdenum, Tungsten, Ruthenium, and Vanadium Catalysts

AbstractThis review article summarizes reports for Z‐selective olefin metathesis reactions by molybdenum, tungsten, ruthenium, and vanadium catalysts. It is clearly demonstrated that the ligand modifications play essential roles in achieving the stereospecific olefin metathesis reactions. In particular, Mo‐ and W‐alkylidene based complex catalysts having pyrrolide‐aryloxide [or bis(aryloxide)] were highly effective in the efficient enantioselective ring opening/cross‐metathesis (EROCM), cross metathesis (CM), homodimerization, ring‐opening metathesis polymerization (ROMP), and in ring closing metathesis (RCM) with high Z‐ selectivities (∼>98%). Ruthenium‐carbene catalysts having cycloadamantyl, catechothiolate, phenolate and thiophenolate ligands display pronounced Z‐selectivity (>98%) in efficient CM, ROCM, AROCM, RCM, ROMP reactions. Halogenated (arylimido)‐alkoxo vanadium‐alkylidenes were thermally robust and effective for efficient highly cis‐specific ROMP of cyclic olefins to afford end‐functionalized ring‐opened polymers.magnified image

Chiral Phosphine Oxide-Catalyzed Enantioselective Ring Opening of Oxetanes

Chiral Phosphine Oxide-Catalyzed Enantioselective Ring Opening of Oxetanes

Cu-Catalyzed Site-Selective and Enantioselective Ring Opening of Cyclic Diaryliodoniums with 1,2,3-Triazoles.

A Cu-catalyzed enantioselective ring-opening/triazolylation reaction is reported. The reaction shows excellent chemoselectivity regarding the three different nitrogen atoms of 1,2,3-triazoles. The optically enriched axially chiral aryl iodides thus obtained were readily derivatized to different types of chiral phosphine ligands and their corresponding copper or palladium complexes.

Hydrogen Bonding Phase-Transfer Catalysis with Ionic Reactants: Enantioselective Synthesis of γ-Fluoroamines.

Ammonium salts are used as phase-transfer catalysts for fluorination with alkali metal fluorides. We now demonstrate that these organic salts, specifically azetidinium triflates, are suitable substrates for enantioselective ring opening with CsF and a chiral bis-urea catalyst. This process, which highlights the ability of hydrogen bonding phase-transfer catalysts to couple two ionic reactants, affords enantioenriched γ-fluoroamines in high yields. Mechanistic studies underline the role of the catalyst for phase-transfer, and computed transition state structures account for the enantioconvergence observed for mixtures of achiral azetidinium diastereomers. The N-substituents in the electrophile influence the reactivity, but the configuration at nitrogen is unimportant for the enantioselectivity.

Catalytic Enantioselective Ring-Opening Reactions of Cyclopropanes.

This review describes the development of enantioselective methods for the ring opening of cyclopropanes. Both approaches based on the reaction of nonchiral cyclopropanes and (dynamic) kinetic resolutions and asymmetric transformations of chiral substrates are presented. The review is organized according to substrate classes, starting by the more mature field of donor-acceptor cyclopropanes. Emerging methods for enantioselective ring opening of acceptor- or donor-only cyclopropanes are then presented. The last part of the review describes the ring opening of more reactive three-membered rings substituted with unsaturations with a particular focus on vinylcyclopropanes, alkylidenecyclopropanes, and vinylidenecyclopropanes. In the last two decades, the field has grown from a proof of concept stage to a broad range of methods for accessing enantioenriched building blocks, and further extensive developments can be expected in the future.

Enantioselective Synthesis of Axially Chiral Biaryls via Copper-Catalyzed Thiolation of Cyclic Diaryliodonium Salts.

Here, we report a chiral copper(II)-bisoxazoline-catalyzed enantioselective ring opening of cyclic diaryliodonium salts with heteroaryl thiols. The readily available 2-mercaptobenzoxazole and 2-mercaptobenzothiazole derivatives reacted efficiently with cyclic diaryliodonium salts and afforded various axially chiral biaryls bearing iodine and sulfur functional groups in excellent yields and enantioselectivities. The products were further transformed into diverse enantiopure alkyl biaryl sulfides, which can be employed as chiral ligands.

Pd‐Catalyzed Enantioselective Ring Opening/Cross‐Coupling and Cyclopropanation of Cyclobutanones

AbstractA palladium‐catalyzed enantioselective sequential ring‐opening/cross‐coupling of cyclobutanones is disclosed that provides chiral indanones bearing C3‐quaternary stereocenters. The reaction process involves palladium‐catalyzed nucleophilic addition of cyclobutanones and aryl halides, enantioselective β‐carbon elimination, and intermolecular trapping of a transient σ‐alkylpalladium complex with boronic acids. Alternatively, an intramolecular cyclopropanation is realized through C−H bond functionalization in the absence of external coupling reagents, affording chiral cyclopropane‐fused‐indanones in good yields and enantioselectivity.