Allenic Aldehydes Research Articles

Synthesis of biologically active heterocyclic compounds from allenic and acetylenic nitriles and related compounds

Abstract Cyclic and polycyclic compounds containing moieties such as imidazole, pyrazole, isoxazole, thiazoline, oxazine, indole, benzothiazole and benzoxazole benzimidazole are prized molecules because of the various pharmaceutical properties that they display. This led Prof. Landor and co-workers to engage in the synthesis of several of them such as alkylimidazolenes, oxazolines, thiazolines, pyrimidopyrimidines, pyridylpyrazoles, benzoxazines, quinolines, pyrimidobenzimidazoles and pyrimidobenzothiazolones. This review covers the synthesis of biologically active heterocyclic compounds by the Michael addition and the double Michael addition of various amines and diamines on allenic nitriles, acetylenic nitriles, hydroxyacetylenic nitriles, acetylenic acids and acetylenic aldehydes. The heterocycles were obtained in one step reaction and in most cases, did not give side products. A brief discussion on the biological activities of some heterocycles is also provided.

Synthesis and odour evaluation of allenic derivatives

AbstractA series of readily available allenic aldehydes and their alcohol, acetate and enol ether derivatives have been prepared and evaluated for their olfactory properties. The tested compounds revealed interesting fruity, floral and woody aspects as the main notes. Copyright © 2015 John Wiley & Sons, Ltd.

ChemInform Abstract: Alkynes as Allylmetal Equivalents in Redox‐Triggered C—C Couplings to Primary Alcohols: (Z)‐Homoallylic Alcohols via Ruthenium‐Catalyzed Propargyl C—H Oxidative Addition.

The cationic ruthenium catalyst generated upon the acid–base reaction of H2Ru(CO)(PPh3)3 and 2,4,6-(2-Pr)3PhSO3H promotes the redox-triggered C–C coupling of 2-alkynes and primary alcohols to form (Z)-homoallylic alcohols with good to complete control of olefin geometry. Deuterium labeling studies, which reveal roughly equal isotopic compositions at the allylic and distal vinylic positions, along with other data, corroborate a catalytic mechanism involving ruthenium(0)-mediated allene–aldehyde oxidative coupling to form a transient oxaruthenacycle, an event that ultimately defines (Z)-olefin stereochemistry.

Alkynes as allylmetal equivalents in redox-triggered C-C couplings to primary alcohols: (Z)-homoallylic alcohols via ruthenium-catalyzed propargyl C-H oxidative addition.

The cationic ruthenium catalyst generated upon the acid–base reaction of H2Ru(CO)(PPh3)3 and 2,4,6-(2-Pr)3PhSO3H promotes the redox-triggered C–C coupling of 2-alkynes and primary alcohols to form (Z)-homoallylic alcohols with good to complete control of olefin geometry. Deuterium labeling studies, which reveal roughly equal isotopic compositions at the allylic and distal vinylic positions, along with other data, corroborate a catalytic mechanism involving ruthenium(0)-mediated allene–aldehyde oxidative coupling to form a transient oxaruthenacycle, an event that ultimately defines (Z)-olefin stereochemistry.

ChemInform Abstract: Rh(I)‐Catalyzed Transformation of Propargyl Vinyl Ethers into (E,Z)‐Dienals: Stereoelectronic Role of trans Effect in a Metal‐Mediated Pericyclic Process and a Shift from Homogeneous to Heterogeneous Catalysis During a One‐Pot Reaction.

The combination of experiments and computations reveals unusual features of stereoselective Rh(I)-catalyzed transformation of propargyl vinyl ethers into (E,Z)-dienals. The first step, the conversion of propargyl vinyl ethers into allene aldehydes, proceeds under homogeneous conditions via a “cyclization-mediated” mechanism initiated by Rh(I) coordination at the alkyne. This path agrees well with the small experimental effects of substituents on the carbinol carbon. The key feature revealed by the computational study is the stereoelectronic effect of the ligand arrangement at the catalytic center. The rearrangement barriers significantly decrease due to the greater transfer of electron density from the catalytic metal center to the CO ligand oriented trans to the alkyne. This effect increases electrophilicity of the metal and lowers the calculated barriers by 9.0 kcal/mol. Subsequent evolution of the catalyst leads to the in situ formation of Rh(I) nanoclusters that catalyze stereoselective tautomerizatio...

In Situ IR and X-ray High Spatial-Resolution Microspectroscopy Measurements of Multistep Organic Transformation in Flow Microreactor Catalyzed by Au Nanoclusters

Analysis of catalytic organic transformations in flow reactors and detection of short-lived intermediates are essential for optimization of these complex reactions. In this study, spectral mapping of a multistep catalytic reaction in a flow microreactor was performed with a spatial resolution of 15 μm, employing micrometer-sized synchrotron-based IR and X-ray beams. Two nanometer sized Au nanoclusters were supported on mesoporous SiO2, packed in a flow microreactor, and activated toward the cascade reaction of pyran formation. High catalytic conversion and tunable products selectivity were achieved under continuous flow conditions. In situ synchrotron-sourced IR microspectroscopy detected the evolution of the reactant, vinyl ether, into the primary product, allenic aldehyde, which then catalytically transformed into acetal, the secondary product. By tuning the residence time of the reactants in a flow microreactor a detailed analysis of the reaction kinetics was performed. An in situ micrometer X-ray absorption spectroscopy scan along the flow reactor correlated locally enhanced catalytic conversion, as detected by IR microspectroscopy, to areas with high concentration of Au(III), the catalytically active species. These results demonstrate the fundamental understanding of the mechanism of catalytic reactions which can be achieved by the detailed mapping of organic transformations in flow reactors.

Rh(I)-Catalyzed Transformation of Propargyl Vinyl Ethers into (E,Z)-Dienals: Stereoelectronic Role of trans Effect in a Metal-Mediated Pericyclic Process and a Shift from Homogeneous to Heterogeneous Catalysis During a One-Pot Reaction

The combination of experiments and computations reveals unusual features of stereoselective Rh(I)-catalyzed transformation of propargyl vinyl ethers into (E,Z)-dienals. The first step, the conversion of propargyl vinyl ethers into allene aldehydes, proceeds under homogeneous conditions via a "cyclization-mediated" mechanism initiated by Rh(I) coordination at the alkyne. This path agrees well with the small experimental effects of substituents on the carbinol carbon. The key feature revealed by the computational study is the stereoelectronic effect of the ligand arrangement at the catalytic center. The rearrangement barriers significantly decrease due to the greater transfer of electron density from the catalytic metal center to the CO ligand oriented trans to the alkyne. This effect increases electrophilicity of the metal and lowers the calculated barriers by 9.0 kcal/mol. Subsequent evolution of the catalyst leads to the in situ formation of Rh(I) nanoclusters that catalyze stereoselective tautomerization. The intermediacy of heterogeneous catalysis by nanoclusters was confirmed by mercury poisoning, temperature-dependent sigmoidal kinetic curves, and dynamic light scattering. The combination of experiments and computations suggests that the initially formed allene-aldehyde product assists in the transformation of a homogeneous catalyst (or "a cocktail of catalysts") into nanoclusters, which in turn catalyze and control the stereochemistry of subsequent transformations.

ChemInform Abstract: Condensation of Prop-2-ynyl Alcohols with 2-Alkylalk-2-enals. A Simple Synthesis of Allenic Aldehydes.

The acid-catalysed condensation of tertiary prop-2-ynyl alcohols with 2-alkylalk-2-enals gave allenic aldehydes 5a–d .

Cationic rhodium(I) complex-catalyzed σ- and π-bond activation cascade: Isomerization of allyl propargyl ethers to allenic aldehydes and dienals

A cationic rhodium(I)/1,1'-bis(diphenylphosphino)ferrocene (dppf) complex catalyzes isomerization of allyl propargyl ethers to allenic aldehydes in good yields at room temperature 40 °C. At 80 °C, carbonyl migration from allenic aldehydes proceeds further to give dienals in good yields. The cationic rhodium(I)/dppf complex acts as a dual catalyst for activation of σ- and π-bonds in these isomerization reactions.

Cationic Rhodium(I)−dppf Complex-Catalyzed Olefin Isomerization/Propargyl Claisen Rearrangement/Carbonyl Migration Cascade

We have established that a cationic rhodium(I)-dppf complex catalyzes isomerizations of allyl propargyl ethers to allenic aldehydes in good yields from room temperature to 40 degrees C. On the other hand, carbonyl migration reactions from allenic aldehydes further proceed to give dienals in good yields at 80 degrees C.

Microwave-Assisted Palladium(0)-Catalyzed Alkylative Cyclization of Allenyl Aldehydes Leading to 3-Substituted 3-Cycloalken-1-ols

We have developed an efficient synthetic method for 3-substituted 3-cyclohexenols and -cyclopentenol based on Pd0-catalyzed alkylative, arylative, alkenylative, alkynylative, and borative cyclization reaction of allene−carbonyl compounds. Microwave irradiation increases not only the reaction rate but also the product yield by suppressing formation of hydroarylation byproducts observed in the same catalytic system. Cyclization of optically active 1,3-disubstituted allene aldehyde reveals that the reaction proceeds not through carbopalladation but through “anti-Wacker”-type oxidative addition.

1,2‐Sulfanyl Group Migration as a Driving Force: New Approach to Pyrroles by Reaction of Allenic Aldehydes with Amines.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Synthesis of Pyrroles from Allenic Aldehydes and Amines

Sulfanyl-substituted allenic aldehydes undergo acid-catalyzed reaction with amines to afford pyrrole derivatives in modest to good yields. The allenic aldehydes are available in a three-step sequence starting with diazoacetates and propargyl sulfides. Although substituent variation in the allenyl aldehyde was insufficiently explored, the reaction provides considerable scope for the construction of highly substituted pyrroles. Two mechanistic pathways are suggested which differ in the manner of 1,2-migration of the sulfanyl group. Both start with the generation of the imine intermediate which undergoes intramolecular cyclization and elimination of the sulfanyl group. In path A, sequential attack of the released sulfanyl group at the iminium carbon and rearomatization leads to the pyrrole product. Path B involves a nucleophilic attack of the imine by the sulfur group and a simultaneous attack of the allene by the nitrogen atom to generate a thiirenium species which then undergoes ring opening and further deprotonation to afford the product.

1,2-Sulfanyl Group Migration as a Driving Force: New Approach to Pyrroles by Reaction of Allenic Aldehydes with Amines

[reaction: see text] Acid-promoted reaction of sulfanyl group substituted allenic aldehyde with amine affords pyrrole derivatives in high yields. The neighboring group participation of the sulfanyl group is the driving force in this transformation.

Regulation of Stereoselectivity Using Lewis Acid in the Cyclization of Allenic Aldehydes Catalyzed by Palladium Complex.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Regulation of Stereoselectivity Using Lewis Acid in the Cyclization of Allenic Aldehydes Catalyzed by Palladium Complex

A highly diastereoselective synthesis of 3 is achieved from the reaction of 1 with hexamethylditin catalyzed by palladium complex in the presence of 20 mol % tris(pentafluorophenyl)borane as a Lewis acid additive for a reversal of diastereoselectivity, whereas 2 is formed in the absence of Lewis acid additive. The method described herein is successful with various substrates 1 in good yields and high levels of diastereoselectivity. [reaction: see text]

ChemInform Abstract: Palladium‐Catalyzed Regio‐ and Diastereoselective Tandem Silastannylation/Allyl Addition of Allene Aldehydes and Allene Ketones: Synthesis of cis Cyclopentanols and Cyclohexanols.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Palladium-Catalyzed Regio- and Diastereoselective Tandem Silastannylation/Allyl Addition of Allene Aldehydes and Allene Ketones: Synthesis ofcis Cyclopentanols and Cyclohexanols

Zwei in einem: Die Palladium-katalysierte regio- und diastereoselektive Silastannylierung von Allenylaldehyden und -ketonen und nachfolgende Allyladdition an die Carbonylgruppe führen zu cis-Cycloalkanolen (siehe Schema; n=1, 2; R=H, CH3; X=NTs, O, C(CO2Et)2 usw.). Dieser Tandemprozess erfordert nur einen einzigen Katalysator und kann bei einheitlich konstanter Temperatur durchgeführt werden. Supporting information for this article is available on the WWW under http://www.angewandte.com or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Palladium-catalyzed regio- and diastereoselective tandem silastannylation/allyl addition of allene aldehydes and allene ketones: synthesis of cis cyclopentanols and cyclohexanols.

Two in one: the palladium-catalyzed regio- and diastereoselective silastannylation of allene aldehydes and ketones and the subsequent allyl addition to the carbonyl group gives rise to cis-cycloalkanols (see scheme; n = 1, 2; R = H, CH3; X = NTs, O, C(CO2Et)2, etc.). This tandem process requires a single catalyst and is carried out at a constant temperature.

Amplification of chirality by transition metal coordination: synthesis of chiral allenes and allene manganese complexes of high enantiomeric purity. Synthesis of methyl (R,E)-(−)-(2,4,5-tetradecatrienoate (pheromone of Acanthoscelides obtectus (say))

The enhancement of the asymmetry of chiral allenes by coordination with a transition metal can be turned to account for (easy) resolution of the complexes and therefore the allenes themselves. This is illustrated here on allene aldehyde complexes of (η-methylcyclopentadienyl) dicarbonylmanganese, possibly bearing a second electron withdrawing substituent, and by the synthesis of an optically active alkenylallenic insect pheromone of high enantiomeric purity.