1,721,075 research outputs found
Regiocontrolled 1,3-Dipolar cycloadditions of nitrile imines with acetylenes and α,β-unsaturated systems: Synthesis of polysubstituted and ring fused pyrazoles with pharmaceutical activity
No full text1,3-Dipolar cycloadditions of nitrile imines with functionalised acetylenes and α,β-unsaturated systems of various sizes have been studied. After cycloaddition, mono- and ring-fused pyrazoles have been obtained. Computational studies allowed a theoretical description of the observed reactivity, in agreement with the experimentally observed regio-chemistry. Selected targeted structures for medicinal applications have been synthetized and in vitro cytotoxicity showed that these pyrazoles can be considered powerful lead compounds for further medicinally relevant targets development
A General Catalytic Enantioselective Transfer Hydrogenation Reaction of β,β-Disubstituted Nitroalkenes Promoted by a Simple Organocatalyst
No full textGiven its synthetic relevance, the catalytic enantioselective reduction of β,β-disubstituted nitroalkenes has received a great deal of attention. Several bio-, metal-, and organo-catalytic methods have been developed, which however are usually applicable to single classes of nitroalkene substrates. In this paper, we present an account of our previous work on this transformation, which implemented with new disclosures and mechanistic insights results in a very general protocol for nitroalkene reductions. The proposed methodology is characterized by (i) a remarkably broad scope encompassing various nitroalkene classes; (ii) Hantzsch esters as convenient (on a preparative scale) hydrogen surrogates; (iii) a simple and commercially available thiourea as catalyst; (iv) user-friendly procedures. Overall, the proposed protocol gives a practical dimension to the catalytic enantioselective reduction of β,β-disubstituted nitroalkenes, offering a useful and general platform for the preparation of nitroalkanes bearing a stereogenic center at the β-position in a highly enantioenriched form. A transition state model derived from control kinetic experiments combined with literature data is proposed and discussed. This model accounts and justifies the observed experimental results
Organocatalysis in the Asymmetric Synthesis of Nitrogen-Containing Compounds: How and Why
Full text linkVarious types of polyfunctionalised stereodefined organic molecules appear to be highly serviceable as organocatalysts in the asymmetric synthesis of nitrogen-containing compounds. Beyond name reactions such as the aza-Henry, the Friedel-Crafts, and the Strecker other representative transformations like the hydrophosphonylation can be easily approached by using the suitable organocatalytic species and are herein reported with a special emphasis placed on the reaction and stereochemical outcomes and on the mechanistic insights
Reversible modulation of the activity of thiourea catalysts with anions: A simple approach to switchable asymmetric catalysis
No full textLeveraging the anion binding properties of thioureas, we show that the activity of known well-performing chiral catalysts can be reduced by coordinating anions (e.g. chloride) and restored by anion metatheses. Three benchmark enantioselective transformations were successfully studied, demonstrating the reversibility of the activation/deactivation processes
Nucleophilic Dearomatization of Activated Pyridines
No full textAmongst nitrogen heterocycles of different ring sizes and oxidation statuses, dihydropyridines (DHP) occupy a prominent role due to their synthetic versatility and occurrence in medicinally relevant compounds. One of the most straightforward synthetic approaches to polysubstituted DHP derivatives is provided by nucleophilic dearomatization of readily assembled pyridines. In this article, we collect and summarize nucleophilic dearomatization reactions of pyridines reported in the literature between 2010 and mid-2018, complementing and updating previous reviews published in the early 2010s dedicated to various aspects of pyridine chemistry. Since functionalization of the pyridine nitrogen, rendering a (transient) pyridinium ion, is usually required to render the pyridine nucleus sufficiently electrophilic to suffer the attack of a nucleophile, the material is organized according to the type of N-functionalization. A variety of nucleophilic species (organometallic reagents, enolates, heteroaromatics, umpoled aldehydes) can be productively engaged in pyridine dearomatization reactions, including catalytic asymmetric implementations, providing useful and efficient synthetic platforms to (enantioenriched) DHPs. Conversely, pyridine nitrogen functionalization can also lead to pyridinium ylides. These dipolar species can undergo a variety of dipolar cycloaddition reactions with electron-poor dipolarophiles, affording polycyclic frameworks and embedding a DHP moiety in their structures
Enantioselective Approaches to 3,4-Annulated Indoles Using Organocatalytic Domino Reactions
No full textOrganocatalytic domino reactions of 4-substituted indoles are summarized in this account. Two reactions have been developed, one with enals, activated by secondary amine catalysts via iminium ions, and one with nitroethene, using a phosphoric acid catalyst. Both reactions required solving the challenge posed by the very low nucleophilicity of the indole substrates, which bear an electron-withdrawing Michael acceptor at C4. DFT calculations were used to shed light on the unique reaction pathway followed by the phosphoric acid catalyzed transformation, wherein a bicoordinated nitronic acid intermediate was found to evolve preferentially through an intramolecular nitro-Michael reaction, instead of the common tautomerization pathway. These reactions provide new and efficient entries to 3,4-ring-fused indoles in diastereo- and enantioenriched form. In more detail, the structures obtained feature a 1,3,4,5-tetrahydrobenzo[ cd ]indole core, which is present in the structural framework of ergot alkaloids. Indeed, the preparation of an intermediate previously used in ergot alkaloid (6,7-secoagroclavine) synthesis was possible from one of the catalytic adducts. 1 Introduction 2 Reactions of 4-Substituted Indoles with α,Î2-Unsaturated Aldehydes Catalyzed by Secondary Amines 3 Reactions of 4-Substituted Indoles with Nitroethene Catalyzed by Bronsted Acids 4 Conclusion
Organocatalytic Enantioselective Transfer Hydrogenation of β-Amino Nitroolefins
No full textThe asymmetric organocatalytic transfer hydrogenation of β-acylamino and β-tert-butyloxycarbonylamino nitroolefins has been successfully realised in excellent enantioselectivities and yields (up to >99% ee, 97% yield) with a simple thiourea catalyst and a Hantzsch ester as hydrogen source, giving a direct access to enantiomerically pure β-amino nitroalkanes. (Figure presented.)
The Emergence of Quinone Methides in Asymmetric Organocatalysis
Full text linkQuinone methides (QMs) are highly reactive compounds that have been defined as “elusive” intermediates, or even as a “synthetic enigma” in organic chemistry. Indeed, there were just a handful of examples of their utilization in catalytic asymmetric settings until some years ago. This review collects organocatalytic asymmetric reactions that employ QMs as substrates and intermediates, from the early examples, mostly based on stabilized QMs bearing specific substitution patterns, to more recent contributions, which have dramatically expanded the scope of QM chemistry. In fact, it was only very recently that the generation of QMs in situ through strategies compatible with organocatalytic methodologies has been realized. This tactic has finally opened the gate to the full exploitation of these unstable intermediates, leading to a series of remarkable disclosures. Several types of synthetically powerful asymmetric addition and cycloaddition reactions, applicable to a broad range of QMs, are now available
An organocatalytic enantioselective direct alpha-heteroarylation of aldehydes with isoquinoline N-oxides
No full textA new protocol for the enantioselective direct alpha-heteroarylation of aldehydes with isoquinoline N-oxides, via chiral enamine catalysis, has been successfully developed. High enantiomeric excesses and moderate to good yields were achieved for a variety of alpha-heteroarylated aldehydes
Sulfoxonium ylides: simple compounds with chameleonic reactivity
No full textSulfur ylides first disclosed in 1930 started to gain more attention in the 1960s, thanks mainly to the studies by Corey and Chaykovsky on their use for the preparation of strained rings. More recently, the chemistry of these compounds has experienced important growth, in part due to the similarity of their reactivities with diazo compounds. This short review provides an overview on the great assortment of reactions of sulfoxonium ylides, outlining a comparison between the chemistry of these ylides and their congeners: sulfonium ylides and diazo compounds. Insertion reactions, cyclisation reactions and ring-opening reactions are highlighted, giving particular attention to catalytic asymmetric methodologies
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