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Oxidative N‐heterocyclic carbene (NHC) organocatalysis, typically leading to the formation of acyl azolium reactive intermediates, constitutes one of the most important activation strategies for the NHC‐catalyzed chemical transformations. Here, we report an unprecedented oxidative radical NHC catalysis by using peroxyester as the external single‐electron oxidant to realize divergent difunctionalization of olefins. The key to success of this chemistry is the catalytic generation of oxygen radicals that could trigger an intermolecular hydrogen atom transfer to activate the inert C−H bonds, thereby enabling the productive radical relay process. With this protocol, commonly used general chemicals could serve as radical precursors to allow efficient synthesis of value‐added products in a straightforward and cost‐effective manner. Preliminary mechanistic investigations, including control experiments and DFT calculations, shed light on the NHC organocatalytic radical reaction mechanism. [ABSTRACT FROM AUTHOR]

Oxidative N‐heterocyclic carbene (NHC) organocatalysis, typically leading to the formation of acyl azolium reactive intermediates, constitutes one of the most important activation strategies for the NHC‐catalyzed chemical transformations. Here, we report an unprecedented oxidative radical NHC catalysis by using peroxyester as the external single‐electron oxidant to realize divergent difunctionalization of olefins. The key to success of this chemistry is the catalytic generation of oxygen radicals that could trigger an intermolecular hydrogen atom transfer to activate the inert C−H bonds, thereby enabling the productive radical relay process. With this protocol, commonly used general chemicals could serve as radical precursors to allow efficient synthesis of value‐added products in a straightforward and cost‐effective manner. Preliminary mechanistic investigations, including control experiments and DFT calculations, shed light on the NHC organocatalytic radical reaction mechanism. [ABSTRACT FROM AUTHOR]

During the past decades, N‐heterocyclic carbene (NHC)‐catalyzed reactions have emerged as a versatile tool in synthetic chemistry. In particular, NHC‐catalyzed cross‐coupling reaction has been significantly developed in many respects, including new reaction development and mechanistic investigation. This concept article presents recent advances towards direct cross‐coupling reactions of aldehydes with alkyl halides enabled by NHC organocatalysis. [ABSTRACT FROM AUTHOR]

Fluorinated ketones are widely prevalent in numerous biologically interesting molecules, and the development of novel transformations to access these structures is an important task in organic synthesis. Herein, we report the multicomponent radical acylfluoroalkylation of a variety of olefins in the presence of various commercially available aromatic aldehydes and fluoroalkyl reagents through N‐heterocyclic carbene organocatalysis. With this protocol, over 120 examples of functionalized ketones with diverse fluorine substituents have been synthesized in up to 99 % yield with complete regioselectivity. The generality of this catalytic strategy was further highlighted by its successful application in the late‐stage functionalization of pharmaceutical skeletons. Excellent diastereoselectivity could be achieved in the reactions forging multiple stereocenters. In addition, preliminary results have been achieved on the catalytic asymmetric variant of the olefin difunctionalization process. [ABSTRACT FROM AUTHOR]

Fluorinated ketones are widely prevalent in numerous biologically interesting molecules, and the development of novel transformations to access these structures is an important task in organic synthesis. Herein, we report the multicomponent radical acylfluoroalkylation of a variety of olefins in the presence of various commercially available aromatic aldehydes and fluoroalkyl reagents through N‐heterocyclic carbene organocatalysis. With this protocol, over 120 examples of functionalized ketones with diverse fluorine substituents have been synthesized in up to 99 % yield with complete regioselectivity. The generality of this catalytic strategy was further highlighted by its successful application in the late‐stage functionalization of pharmaceutical skeletons. Excellent diastereoselectivity could be achieved in the reactions forging multiple stereocenters. In addition, preliminary results have been achieved on the catalytic asymmetric variant of the olefin difunctionalization process. [ABSTRACT FROM AUTHOR]

In this account, we describe our recent developments in organocatalyzed asymmetric methodologies for the practical synthesis of both enantiomers. The synthesis of both enantiomeric products by using both enantiomeric catalysts is the most traditional way. In addition, use of two pseudoenantiomeric catalysts provides a more practical approach for the synthesis of both enantiomeric products. Even more efficient is the use of a single enantiomeric catalyst in the presence or absence of certain additives for obtaining both enantiomeric products. These three different strategies are illustrated by using certain organocatalyzed asymmetric approaches. [ABSTRACT FROM AUTHOR]

Two chiral carboxylic acid functionalized micro- and mesoporous metal-organic frameworks (MOFs) are constructed by the stepwise assembly of triple-stranded heptametallic helicates with six carboxylic acid groups. The mesoporous MOF with permanent porosity functions as a host for encapsulation of an enantiopure organic amine catalyst by combining carboxylic acids and chiral amines in situ through acid-base interactions. The organocatalyst-loaded framework is shown to be an efficient and recyclable heterogeneous catalyst for the asymmetric direct aldol reactions with significantly enhanced stereoselectivity in relative to the homogeneous organocatalyst. [ABSTRACT FROM AUTHOR]

Two chiral carboxylic acid functionalized micro- and mesoporous metal-organic frameworks (MOFs) are constructed by the stepwise assembly of triple-stranded heptametallic helicates with six carboxylic acid groups. The mesoporous MOF with permanent porosity functions as a host for encapsulation of an enantiopure organic amine catalyst by combining carboxylic acids and chiral amines in situ through acid-base interactions. The organocatalyst-loaded framework is shown to be an efficient and recyclable heterogeneous catalyst for the asymmetric direct aldol reactions with significantly enhanced stereoselectivity in relative to the homogeneous organocatalyst. [ABSTRACT FROM AUTHOR]

The article presents information on the asymmetric synthesis of bicyclic amino acids which are important in peptide based drug designing. The bicyclic amino acid also forms a core structure of telaprevir which is a protease inhibitor of hepatitis C virus. The Phase transfer catalyzed conjugate addition reaction is used to synthesis bicyclic amino acid of telaprevir.

Innentitelbild: Radical Acylfluoroalkylation of Olefins through N-Heterocyclic Carbene Organocatalysis (Angew. B Die Mehrkomponenten-Acylfluoralkylierung b von Olefinen durch NHC-Organokatalyse (NHC=N-heterocyclisches Carben) wird im Forschungartikel von J.-L. Li, B. Han, Q.-Z. Die Allgemeingültigkeit der Methode wird durch die Modifizierung pharmazeutischer Gerüste in späten Synthesestadien unterstrichen. [Extracted from the article]

The efficacy and synthetic versatility of asymmetric organocatalysis have contributed enormously to the field of organic synthesis since the early 2000s. As asymmetric organocatalytic methods mature, they have extended beyond the academia and undergone scale-up for the production of chiral drugs, natural products, and enantiomerically enriched bioactive molecules. This review provides a comprehensive overview of the applications of asymmetric organocatalysis in medicinal chemistry. A general picture of asymmetric organocatalytic strategies in medicinal chemistry is firstly presented, and the specific applications of these strategies in pharmaceutical synthesis are systematically described, with a focus on the preparation of antiviral, anticancer, neuroprotective, cardiovascular, antibacterial, and antiparasitic agents, as well as several miscellaneous bioactive agents. The review concludes with a discussion of the challenges, limitations and future prospects for organocatalytic asymmetric synthesis of medicinally valuable compounds. [ABSTRACT FROM AUTHOR]

Site‐specifically deuterated organocatalysts were prepared and found to show improved reactivity over the non‐deuterated analogs. Two privileged C2‐symmetric chiral binaphthyl‐modified tetraalkylammonium salts were selected for this study. The stability of these phase‐transfer catalysts was generally improved by site‐specific deuteration, though the degree of improvement was structure dependent. In particular, a large secondary kinetic isotope effect was observed for the tetradeuterated phase‐transfer catalyst. The performance of these deuterated catalysts in the asymmetric catalytic alkylation of amino acid derivatives was better than that of non‐deuterated analogs at low catalyst loadings. The results suggest that catalyst deuteration is a promising strategy for enhancing the stability and performance of organocatalysts. [ABSTRACT FROM AUTHOR]

The article presents chemical equations related to the article"Enantioselective Synthesis of Biologically Important Spiro[indoline-3,2'-quinazolines] via Catalytic Asymmetric Isatin-Involved Tandem Reactions" by Y. Jiang and others, published in the periodical " Tetrahedron: Asymmetry" in 2013.

The direct functionalization of inert C(sp3)−H bonds under environmentally benign catalytic conditions remains a challenging task in synthetic chemistry. Here, we report an organocatalytic remote C(sp3)−H acylation of amides and cascade cyclization through a radical‐mediated 1,5‐hydrogen atom transfer mechanism using N‐heterocyclic carbene as the catalyst. Notably, a diversity of nitrogen‐containing substrates, including simple linear aliphatic carbamates and ortho‐alkyl benzamides, can be successfully applied to this organocatalytic system. With the established protocol, over 120 examples of functionalized δ‐amino ketones and isoquinolinones with diverse substituents were easily synthesized in up to 99 % yield under mild conditions. The robustness and generality of the organocatalytic strategy were further highlighted by the successful acylation of unactivated C(sp3)−H bonds and late‐stage modification of pharmaceutical molecules. Then, the asymmetric control of the radical reaction was attempted and proven feasible by using a newly designed chiral thiazolium catalyst, and moderate enantioselectivity was obtained at the current stage. Preliminary mechanistic investigations including several control reactions, KIE experiments, and computational studies shed light on the organocatalytic radical reaction mechanism. [ABSTRACT FROM AUTHOR]

The direct functionalization of inert C(sp3)−H bonds under environmentally benign catalytic conditions remains a challenging task in synthetic chemistry. Here, we report an organocatalytic remote C(sp3)−H acylation of amides and cascade cyclization through a radical‐mediated 1,5‐hydrogen atom transfer mechanism using N‐heterocyclic carbene as the catalyst. Notably, a diversity of nitrogen‐containing substrates, including simple linear aliphatic carbamates and ortho‐alkyl benzamides, can be successfully applied to this organocatalytic system. With the established protocol, over 120 examples of functionalized δ‐amino ketones and isoquinolinones with diverse substituents were easily synthesized in up to 99 % yield under mild conditions. The robustness and generality of the organocatalytic strategy were further highlighted by the successful acylation of unactivated C(sp3)−H bonds and late‐stage modification of pharmaceutical molecules. Then, the asymmetric control of the radical reaction was attempted and proven feasible by using a newly designed chiral thiazolium catalyst, and moderate enantioselectivity was obtained at the current stage. Preliminary mechanistic investigations including several control reactions, KIE experiments, and computational studies shed light on the organocatalytic radical reaction mechanism. [ABSTRACT FROM AUTHOR]

A catalytic asymmetric direct Michael reaction of ketones with trans‐β‐arylnitroethenes can be achieved under the influence of optically pure L‐hydroxyproline‐based secondary‐amino aromatic Tf‐amide organocatalyst. The effect of the trialkylamine base additive such as diethylmethylamine is of paramount importance to accomplish high reactivity and enantioselectivity in this asymmetric Michael reaction. [ABSTRACT FROM AUTHOR]

An organocatalytic vinylogous Michael addition triggered triple-cascade reaction has been developed. 2-Hydroxycinnamaldehydes worked under iminium activation with either acyclic or cyclic ketone-derived α,α-dicyanoalkenes, yielding the benzofused oxabicyclo[3.3.1]nonanes bearing one quaternary stereocenter with excellent stereoselectivities. [ABSTRACT FROM AUTHOR]

An organocatalytic multicomponent reaction of N-protected hydroxylamines, acrylaldehyde and acetal-containing enones was developed. Bisacetal-containing bicyclic isoxazolidine derivatives bearing four continuous stereocenters were formed with excellent stereoselectivities. A plausible reaction pathway was proposed based on 18O-labeling control experiments. [ABSTRACT FROM AUTHOR]

Based on an efficient method for in situ generation of N-o-QM species in the presence of a base, enantioselective catalytic conjugated additions of tritylthiol to in situ generated N-o-QMs are reported. Acid–base bifunctional organocatalyst 4c (10 mol%) enables these transformations with high stereoselectivities (up to 94% ee) using H2O/DCM as a solvent under mild conditions. [ABSTRACT FROM AUTHOR]

Asymmetric catalysis, deuteration, kinetic isotope effects, organocatalysis, phase-transfer catalysis Keywords: asymmetric catalysis; deuteration; kinetic isotope effects; organocatalysis; phase-transfer catalysis EN asymmetric catalysis deuteration kinetic isotope effects organocatalysis phase-transfer catalysis 1 1 1 09/25/23 20230921 NES 230921 B Incorporating deuteriums into the correct positions of organocatalysts b increases their stability and robustness, just like the story of "The Three Little Pigs": the first two pigs hastily construct houses made of straw and sticks (non-deuterated and dideuterated catalysts), but they were quickly destroyed by the wolf's huffing and puffing (OH SP - sp ). Cover Feature: Impact of Catalyst Deuteration on the Reactivity of Chiral Phase-Transfer Organocatalysts (Chem. Eur. J. 53/2023). [Extracted from the article]

We report herein a dynamic kinetic resolution (DKR) involving ortho-quinone methide ( o-QM) intermediates. In the presence of Et3N and the cinchonine-derived nucleophilic catalyst D, the DKR of 2-sulfonylalkyl phenols with allenic esters afforded chiral benzylic sulfones in 57-79 % yield with good to excellent enantioselectivity (85-95 % ee). Furthermore, with 2-(tosylmethyl)sesamols or 2-(tosylmethyl)naphthols, from which stable o-QM substrates can be generated, a formal [4+2] cycloaddition delivered 4-aryl- or alkyl-substituted chromans with excellent enantioselectivity (88-97 % ee). [ABSTRACT FROM AUTHOR]

The asymmetric synthesis of 3- sec-substituted pyrrole derivatives through vinylogous imine intermediates generated in situ from 2,5-dimethyl-3-[1-(arylsulfonyl)alkyl]pyrroles with high activity and enantioselectivity (up to 98 % ee) was examined. Employing a cinchona alkaloid based chiral bifunctional organocatalyst, the reaction of tritylthiol to sulfonylpyrroles delivered a series of highly enantioselective sulfur-containing 3- sec-substituted pyrroles. [ABSTRACT FROM AUTHOR]

The enantioselective conjugated addition of tritylthiol to in situ generated ortho-quinone methides ( o-QMs) is catalyzed by an acid-base bifunctional squaramide organocatalyst. The transformation proceeds with high yield (up to 99 %) and stereoselectivity (up to 97:3 e.r.) using water as solvent under mild conditions. The catalyst system provides a new strategy for the synthesis of optically active benzyl mercaptans. Control experiments suggested that o-QMs are generated by the tertiary amine moiety of the squaramide organocatalyst and that the water-oil biphase is crucial for achieving high reactivity and stereoselectivity. [ABSTRACT FROM AUTHOR]

A series of of amphiphilic imidazole based secondary and primary amine catalysts were synthesized and shown to be very effective with an acid cocatalyst for the asymmetric reaction of cyclohexanone to β, γ-unsaturated α-keto ester. Interestingly, primary and secondary amine catalysts show different regio-selectivities in this reaction. Under the catalysis of secondary amine 1, excellent enantioselectivities were observed for the products from direct 3+3 reactions of cyclohexanone with β, γ-unsaturated α-keto esters using water as the solvent. Moreover, the same reactants catalyzed by the primary amines 2 lead to the aldol reactions, affording the corresponding products with high diastereoselectivities and up to 97% ee. Theoretical studies on the transition states by using a model in gas phase revealed that steric effect plays an important role on different chemo-selective induction between the secondary amine 1 and primary amine 2. [ABSTRACT FROM AUTHOR]

Unprecedented organocatalyzed asymmetric cascade reactions have been developed for the facile synthesis of chiral spirooxindole-based isotetronic acids and 5-1 H-pyrrol-2-ones.The asymmetric 1,2-addition reactions of α-ketoesters to isatins and imines by using an acid-base bifunctional 6′-OH cinchona alkaloid catalyst, followed by cyclization and enolization of the resulting adducts, gave chiral spiroisotetronic acids and 5-1 H-pyrrol-2-ones, respectively, in excellent optical purities (up to 98 % ee). FT-IR analysis supported the existence of hydrogen-bonding interaction between the 6′-OH group of the cinchona catalyst and an isatin carbonyl group, an interaction that might be crucial for catalyst activity and stereocontrol. [ABSTRACT FROM AUTHOR]

For the first time a direct asymmetric aldol reaction of free hydroxyacetone and activated ketones is achieved by using the new title catalyst. [ABSTRACT FROM AUTHOR]

Mechanistic investigations, including control reactions, KIE experiments, and computational studies, shed light on the organocatalytic radical reaction mechanism. Cover Picture: Remote C(sp3)-H Acylation of Amides and Cascade Cyclization via N-Heterocyclic Carbene Organocatalysis (Angew. Keywords: Cyclization Reactions; C-H Functionalization; Isoquinolinone; NHC Organocatalysis; Radical Acylation EN Cyclization Reactions C-H Functionalization Isoquinolinone NHC Organocatalysis Radical Acylation 1 1 1 03/30/22 20220404 NES 220404 B An NHC-organocatalyzed b remote C(sp SP 3 sp )-H acylation of amides is developed based on a 1,5-hydrogen atom transfer strategy. [Extracted from the article]

Titelbild: Remote C(sp3)-H Acylation of Amides and Cascade Cyclization via N-Heterocyclic Carbene Organocatalysis (Angew. Cyclization Reactions, C-H Functionalization, Isoquinolinone, NHC Organocatalysis, Radical Acylation Keywords: Cyclization Reactions; C-H Functionalization; Isoquinolinone; NHC Organocatalysis; Radical Acylation EN Cyclization Reactions C-H Functionalization Isoquinolinone NHC Organocatalysis Radical Acylation 1 1 1 03/30/22 20220404 NES 220404 B Eine organokatalytische b C(sp SP 3 sp )-H-Acylierung von Amiden wurde auf der Grundlage einer 1,5-Wasserstoffatom-Transferstrategie entwickelt. [Extracted from the article]

This stereoselective method relies on an organo-catalyzed asymmetric Diels-Alder reaction/iminium ion-induced cyclization sequence. [ABSTRACT FROM AUTHOR]

Vinylogous imine intermediates generated in situ from sulfonylindoles undergo asymmetric 1,4-addition with trityl mercaptan (I) to form the title compounds with good to excellent enantioselectivities. [ABSTRACT FROM AUTHOR]

The enantioselective conjugated addition of tritylthiol to in situ generated ortho-quinone methides in the presence of a squaramide organocatalyst is studied. [ABSTRACT FROM AUTHOR]

Amphiphilic imidazole based secondary and primary amine catalysts show different chemoselectivity in the title reaction. [ABSTRACT FROM AUTHOR]

The article presents chemical equations related to the article "Synthesis of Chiral Spirooxindole-Based Isotetronic Acids and 5-1H-Pyrrol-2-ones Through Cascade Reactions with Bifunctional Organocatalysts" by W. Guo and others, published in the periodical "Chemistry-A European Journal" in 2014.

The new title organocatalyst forms an emulsion system in the reaction mixture through self-assembly. [ABSTRACT FROM AUTHOR]