Regulating iminophosphorane PN bond reactivity through geometric constraints with cage-shaped triarylphosphines.

Structure-reactivity investigations and quantum-chemical parametrization of steric and electronic properties of geometrically constrained iminophosphoranes enabled the design of new frustrated Lewis pairs and revealed unusual properties at the phosphonium center embedded in the cage-shaped triptycene tricyclic scaffold.

Reactivity and Steric Parameters from 2D to 3D Bulky Pyridines: Increasing Steric Demand at Nitrogen with Chiral Azatriptycenes.

Sterically hindered pyridines embedded in a three-dimensional triptycene framework have been synthesized, and their resolution by chiral HPLC enabled access to unprecedented enantiopure pyridines exceeding the known steric limits. The design principles for new axially chiral pyridine derivatives are then described. To rationalize their associations with Lewis acids and transition metals, a comprehensive determination of the steric and electronic parameters for this new class of pyridines was performed.

One-Carbon Homologation of Knoevenagel Adducts: Enantioselective Access to Benzhydryl Derivatives.

A one-carbon homologation of Knoevenagel adducts enabling the insertion of a CHAr fragment is reported. The strategy involves a sulfur ylide mediated cyclopropanation followed by the rearrangement of cyclopropanes and enables the synthesis of a series of benzhydryl derivatives. Mechanistic studies reveal that the cyclopropane rearrangement involves a Lewis acid catalyzed ring-opening followed by the 1,2-migration of an aryl group.

Chiral Isochalcogenourea-Catalysed Enantioselective (4+2) Cycloadditions of Allenoates.

Allenoates are versatile building blocks which are primarily activated and controlled using chiral tert. phosphine and tert. amine Lewis bases.

Chiral Isochalcogenourea-Catalysed Enantioselective (4+2) Cycloadditions of Allenoates.

Allenoates are versatile building blocks which are primarily activated and controlled using chiral tert. phosphine and tert. amine Lewis bases.

Cycloaddition of cyclopropanes for the elaboration of medium-sized carbocycles.

The stereocontrolled formation of medium-sized carbocycles is a major goal in modern organic chemistry due to their widespread occurrence in natural products and pharmaceutically active ingredients. One approach consists in the use of cycloaddition reactions which notably results in high selectivities and atom-economy. To this end, cyclopropanes are ideal substrates since they can provide readily functionalized three- or five-carbon synthons.

Sterically hindered ortho-substituted phosphatriptycenes as configurationally stable P-chirogenic triarylphosphines.

ortho-Substituted and unsymmetrical 9-phospha-triptycenes were synthesized via two synthetic approaches involving densely functionalized ortho-halogenated triarylmethane or phosphine precursors. ortho-Substituents imposed a considerable steric shielding due to the tricyclic cage-shaped structure with the aryl rings p-systems orthogonal to the phosphorus electron pair. A series of Au(i) and Rh(i) complexes were analysed in the solid state to determine Tolman electronic parameters, cone angles and buried volumes of these unprecedented functionalized phosphines.

Synthesis and characterization of a 5-membered ring cyclic hydroxylamine coupled to triphenylphosphonium to detect mitochondrial superoxide by EPR spectrometry.

As mitochondrial superoxide is becoming an attractive metabolic and pharmacological target, there is an important need for developing analytical tools able to detect superoxide with high sensitivity and specificity. Among EPR-based methods, it has been recently reported that cyclic hydroxylamines offer a high sensitivity to measure superoxide production. Here, we report the synthesis and evaluation of mitoCPH, in which a 5-membered ring hydroxylamine was coupled to a triphenylphosphonium moiety to allow mitochondrial accumulation.

Complementary Synthetic Approaches toward 9-Phosphatriptycene and Structure-Reactivity Investigations of Its Association with Sterically Hindered Lewis Acids.

Two practical and high-yielding syntheses of 9-phosphatriptycene are reported. In both approaches, the key step is based on the cyclization of a (tris)lithio-triphenylmethane or a (tris)lithio-triphenylphosphine intermediate on a phosphorus or a carbon electrophile, respectively. The association of 9-phosphatriptycene with representative boron- and carbon-centered Lewis acids was investigated by IR, NMR, and UV-vis titration experiments and by computational methods, shedding light on its steric hindrance, σ-donating ability, and Brønsted and Lewis basicities.

First Evidence of the Cysteine and Glutathione Conjugates of 3-Sulfanylpentan-1-ol in Hop ( Humulus lupulus L.).

After evidence of the cysteinylated precursors of 3-sulfanyl-4-methylpentan-1-ol (Cys-26) and 3-sulfanylhexan-1-ol (Cys-23) in hop, S-glutathione precursors (G-23 and G-26) were recently discovered in different dual-purpose hop varieties. Because free 3-sulfanylpentan-1-ol (21) has also been detected in hop, the present work aimed to identify its potential precursors. The compounds S-3-(1-hydroxylpentyl)cysteine (Cys-21) and S-3-(1-hydroxylpentyl)glutathione (G-21) were first synthesized and characterized by nuclear magnetic resonance and high-resolution mass spectrometry.

Highly ( Z)-Diastereoselective Synthesis of Trifluoromethylated exo-Glycals via Photoredox and Copper Catalysis.

Highly ( Z)-diastereoselective approaches for the synthesis of trifluoromethylated exo-glycals by copper and photoredox catalysis are described. These complementary reactions are applicable to a wide range of methylene exo-glycals generated from the corresponding pyranoses and furanoses and give trifluoromethylated compounds under mild conditions in moderate to good yields. DFT calculations have allowed a rationalization of the observed ( Z)-stereoselectivity.

Syntheses of Highly Functionalized Spirocyclohexenes by Formal [4+2] Annulation of Arylidene Azlactones with Allenoates.

A straightforward phosphine-catalyzed formal [4+2] annulation between α-branched allenoates and arylidene azlactones has been developed to access highly functionalized spirocyclohexenes. This cyclization favors the γ-addition of the phosphine-activated allenoates over a β'-addition pathway. Detailed computational studies support the proposed mechanism and provide a reasonable explanation for the observed regioselectivity and the noted effect of the catalyst.

Synthesis of Cyclic Organic Carbonates Using Atmospheric Pressure CO and Charge-Containing Thiourea Catalysts.

Cycloadditions of epoxides with CO to synthesize cyclic five-membered ring organic carbonates are of broad interest from a synthetic, environmental, and green chemistry perspective, and the development of effective catalysts for these transformations is an ongoing challenge. A series of eight charge-containing thiourea salts that catalyze these reactions under mild conditions (i.e.

Asymmetric Sulfur-Ylide-Mediated Formal [4+1]-Annulation Reaction: Scope and Mechanism.

A formal [4+1]-annulation strategy between sulfur ylides and 1,3-dienes was developed to afford functionalized cyclopentanoids. The process consists of a stereoselective cyclopropanation reaction followed, in situ, by a stereospecific MgI -catalyzed vinylcyclopropane-cyclopentene rearrangement. The use of chiral sulfur ylides provided cyclopentanoids with excellent enantiocontrol.

Effective Antimalarial Activities of α-Hydroxy Diynes Isolated from Ongokea gore.

Three diynes, octadec-17-ene-9,11-diynoate ethyl (1: ), 8-hydroxy-octadeca-13,17-diene-9,11-diynoate ethyl (2: ), and 8-hydroxy-octadec-13-ene-9,11-diynoate ethyl (3: ), were isolated from seed oil. The structure assignment of these three compounds was based according to chemical and spectroscopic data. They were screened against , the parasite that causes malaria.

Origin of the E/Z Selectivity in the Synthesis of Tetrasubstituted Olefins by Wittig Reaction of α-Fluorophosphonium Ylides: An Explanation for the Low Stereoselectivity Observed in Reactions of α-Alkoxy Aldehydes.

A series of tetrasubstituted fluoroalkenes were synthesized in good yield and high E/Z selectivity (up to 96/4) by Wittig reaction between α-heterosubstituted ketones and α-fluorophosphonium ylides. A detailed study of factors that control stereoselectivity in these reactions shows that stereoselectivity is the result of stabilizing CH···F and N···C═O interactions in the addition TS leading to the E isomer. This analysis provides a rationale for the observed decrease in selectivity for reactions of stabilized ylides with α-alkoxy aldehydes.

Asymmetric Synthesis of 2,3-Dihydrobenzofurans by a [4+1] Annulation Between Ammonium Ylides and In Situ Generated o-Quinone Methides.

A highly enantio- and diastereoselective [4+1] annulation between in situ generated ammonium ylides and o-quinone methides for the synthesis of a variety of 2,3-dihydrobenzofurans has been developed. The key factors controlling the reactivity and stereoselectivity were systematically investigated by experimental and computational means and the energy profiles obtained provide a deeper insight into the mechanistic details of this reaction.

On the origin of the stereoselectivity in chiral amide-based ammonium ylide-mediated epoxidations.

Abstract: Detailed DFT studies provide an in-depth mechanistic understanding for the use of chiral amide-based ammonium ylides in epoxidation reactions. It is shown that the used chiral auxiliary efficiently shields one face of the ylide, which thus results in an extraordinarily high stereoselectivity giving only one trans-isomer with perfect control of the absolute configuration.

3-Sulfanyl-4-methylpentan-1-ol in Dry-Hopped Beers: First Evidence of Glutathione S-Conjugates in Hop (Humulus lupulus L.).

Monovarietal dry-hopped beers were produced with the dual-purpose hop cultivars Amarillo, Hallertau Blanc, and Mosaic. The grapefruit-like 3-sulfanyl-4-methylpentan-1-ol was found in all three beers at concentrations much higher than expected on the basis of the free thiol content in hop. Even cysteinylated precursors proved unable to explain our results.

Benzylic Ammonium Ylide Mediated Epoxidations.

A high yielding synthesis of stilbene oxides using ammonium ylides has been developed. It turned out that the amine leaving group plays a crucial role as trimethylamine gives higher yields than DABCO or quinuclidine. The amine group also influences the diastereoselectivity, and detailed DFT calculations to understand the key parameters of these reactions have been carried out.

Towards a General Understanding of Carbonyl-Stabilised Ammonium Ylide-Mediated Epoxidation Reactions.

The key factors for carbonyl-stabilised ammonium ylide-mediated epoxidation reactions were systematically investigated by experimental and computational means and the hereby obtained energy profiles provide explanations for the observed experimental results. In addition, we were able to identify the first tertiary amine-based chiral auxiliary that allows for high enantioselectivities and high yields for such epoxidation reactions.

Activation of the SN2 Reaction by Adjacent π Systems: The Critical Role of Electrostatic Interactions and of Dissociative Character.

The activation of the SN2 reaction by π systems is well documented in textbooks. It has been shown previously that this is not primarily due to classical (hyper)conjugative effects. Instead, π-conjugated substituents enhance favorable substrate-nucleophile electrostatic interactions, with electron-withdrawing groups (EWG) on the sp(2) system leading to even stronger activation.

Formal Asymmetric (4+1) Annulation Reaction between Sulfur Ylides and 1,3-Dienes.

A highly enantioselective synthesis of functionalized cyclopentanoids by a formal asymmetric (4+1) annulation strategy was developed. The methodology consists of a stereoselective cyclopropanation reaction between chiral sulfur ylides and 1,3-dienes followed by a, in situ, stereospecific MgI2 -catalyzed rearrangement of vinylcyclopropanes. This method is distinguished by a remarkable compatibility with functional groups and a high stereocontrol.

Isolation of a series of fatty acid components of Ongokea gore seed (Isano) oil and their detailed structural analysis.

The total oil production capacity of isano oil is estimated at about 10,000 tons annually. Previous studies of this oil revealed that it is rich in fatty acids including a conjugated diyne moiety. This makes isano oil an excellent candidate for sustainable applications development.

Asymmetric syntheses of three-membered heterocycles using chiral amide-based ammonium ylides.

The use of carbonyl-stabilised ammonium ylides to access chiral glycidic amides and the corresponding aziridines has so far been limited to racemic trans-selective protocols. We herein report the development of an asymmetric approach to access such compounds with high levels of stereoselectivity using easily accessible chiral auxiliary-based ammonium ylides. The use of phenylglycinol as the chiral auxiliary was found to be superior to Evans or pseudoephedrine-based auxiliaries resulting in good to excellent stereoselectivities in both, epoxidation and aziridination reactions.