Propargylic Ketones Research Articles

Umpolung coupling of pyridine-2-carboxaldehydes and propargylic carbonates via N-heterocyclic carbene/palladium synergetic catalysis.

The umpolung cross-coupling reaction of pyridine-2-carboxaldehydes and propargylic carbonates has been developed for the first time through N-heterocyclic carbene/palladium cooperative catalysis with the judicious selection of the palladium catalyst, ligand and N-heterocyclic carbene, giving the propargylic ketones regioselectively.

Mechanochemical Synthesis of 1,2,6-Thiadiazine 1-Oxides from Sulfonimidamides and the Fluorescence Properties of the Products.

A solvent-free mechanochemical synthesis for 1,2,6-thiadiazine 1-oxides starting from NH-sulfonimidamides and propargyl ketones has been developed. Lewis acids affect these one-pot aza-Michael-addition/cyclization/dehydration reaction sequences. The photophysical properties of the resulting heterocyclic sulfonimidamide derivatives were characterized.

1,2,6-Thiadiazine 1-Oxides: Unsaturated Three-Dimensional S,N-Heterocycles from Sulfonimidamides.

Unprecedented three-dimensional 1,2,6-thiadiazine 1-oxides have been prepared by an aza-Michael-addition/cyclization/condensation reaction sequence starting from sulfonimidamides and propargyl ketones. The products have been further functionalized by standard cross-coupling reactions, selective bromination of the heterocyclic ring, and conversion into a β-hydroxy substituted derivative. A representative product was characterized by single-crystal X-ray structure analysis.

Laccase‐mediated Oxidations of Propargylic Alcohols. Application in the Deracemization of 1‐arylprop‐2‐yn‐1‐ols in Combination with Alcohol Dehydrogenases

AbstractThe catalytic system composed by the laccase from Trametes versicolor and the oxy‐radical TEMPO has been successfully applied in the sustainable oxidation of fourteen propargylic alcohols. The corresponding propargylic ketones were obtained in most cases in quantitative conversions (87–>99 % yield), demonstrating the efficiency of the chemoenzymatic methodology in comparison with traditional chemical oxidants, which usually lead to problems associated with the formation of by‐products. Also, the stereoselective reduction of propargylic ketones was studied using alcohol dehydrogenases such as the one from Ralstonia species overexpressed in E. coli or the commercially available evo‐1.1.200, allowing the access to both alcohol enantiomers mostly with complete conversions and variable selectivities depending on the aromatic pattern substitution (97–>99 % ee). To demonstrate the compatibility of the laccase‐mediated oxidation and the alcohol dehydrogenase‐catalyzed bioreduction, a deracemization strategy starting from the racemic compounds was developed through a sequential one‐pot two‐step process, obtaining a selection of (S)‐ or (R)‐1‐arylprop‐2‐yn‐1‐ols with excellent yields (>98 %) and selectivities (>98 % ee) depending on the alcohol dehydrogenase employed.

Synthesis of the C6–C18 bis-tetrahydrofuran fragment of the proposed structure of iriomoteolide-2a via stepwise double SN2 cyclization reactions

The C6–C18 bis-tetrahydrofuran (bis-THF) fragment of the proposed structure of iriomoteolide-2a has been synthesized via stepwise double intramolecular SN2-type etherifications. The C11 and C16 stereogenic centers could be secured in the forms of propargyl alcohols by asymmetric transfer hydrogenation of the corresponding propargyl ketones. The C9–C12 THF ring was first constructed via a tandem asymmetric dihydroxylation (AD)–SN2 sequence while the C13–C16 THF ring was later installed via an intramolecular SN2 reaction of a chiral propargyl mesylate. During the latter THF ring formation, epimerization at the propargylic carbon was not observed. Since the initially proposed (9R,11S,12R) configuration of iriomoteolide-2a has recently been revised to (9S,11R,12S), the established synthesis of the C6–C18 bis-THF fragment could be easily amended by using the opposite enantiomers of the chiral ligands for AD and asymmetric transfer hydrogenation.

Third‐Generation Amino Acid Furanoside‐Based Ligands from d‐Mannose for the Asymmetric Transfer Hydrogenation of Ketones: Catalysts with an Exceptionally Wide Substrate Scope

AbstractA modular ligand library of α‐amino acid hydroxyamides and thioamides was prepared from 10 different N‐tert‐butyloxycarbonyl‐protected α‐amino acids and three different amino alcohols derived from 2,3‐O‐isopropylidene‐α‐d‐mannofuranoside. The ligand library was evaluated in the half‐sandwich ruthenium‐ and rhodium‐catalyzed asymmetric transfer hydrogenation of a wide array of ketone substrates, including simple as well as sterically demanding aryl alkyl ketones, aryl fluoroalkyl ketones, heteroaromatic alkyl ketones, aliphatic, conjugated and propargylic ketones. Under the optimized reaction conditions, secondary alcohols were obtained in high yields and in enantioselectivities up to >99%. The choice of ligand/catalyst allowed for the generation of both enantiomers of the secondary alcohols, where the ruthenium‐hydroxyamide and the rhodium‐thioamide catalysts act complementarily towards each other. The catalytic systems were also evaluated in the tandem isomerization/asymmetric transfer hydrogenation of racemic allylic alcohols to yield enantiomerically enriched saturated secondary alcohols in up to 98% ee. Furthermore, the catalytic tandem α‐alkylation/asymmetric transfer hydrogenation of acetophenones and 3‐acetylpyridine with primary alcohols as alkylating and reducing agents was studied. Secondary alcohols containing an elongated alkyl chain were obtained in up to 92% ee.magnified image

Convergent Synthesis of the Dihydropyran Core Containing the C1-C15 Subunit of Sorangicin A Employing Gold(I)-Catalyzed Cyclization of an Allenic Alcohol.

A convergent route to the C1-C15 subunit of sorangicin A is disclosed. The key steps include carbon-carbon bond formation using an α-chloro sulfide, regioselective hydrozirconation of an internal alkyne for the preparation of a trisubstituted iodoalkene, allene formation using the Myers-Movassaghi protocol, stereoselective reduction of allylic and propargylic ketones using Noyori's catalyst, and gold(I)-catalyzed cyclization of a β-hydroxy allene to construct the dihydropyran ring.

ChemInform Abstract: TEMPO‐Catalyzed Synthesis of 5‐Substituted Isoxazoles from Propargylic Ketones and TMSN3.

A novel and efficient TEMPO-catalyzed synthesis of 5-substituted isoxazoles from propargylic ketones and TMSN3 via a radical mechanism process is described. This methodology provides an easy access to a variety of useful 5-substituted isoxazoles from simple and readily available propargylic ketones and TMSN3 in good to excellent yields. A plausible reaction mechanism for this process is proposed.

ChemInform Abstract: 1,2‐Thiazines: One‐Pot Syntheses Utilizing Mono and Diaza Analogues of Sulfones.

AbstractA one‐pot Michael addition/cyclization/condensation reaction sequence for the regioselective synthesis of 1,2‐thiazines is developed, starting from propargyl ketones and NH‐sulfoximines or NH‐sulfondiimines.

Synthesis of Pyrazoles via Electrophilic Cyclization of Alkynes Containing Thiophene

Background: Pyrazole is a simple aromatic ring an organic compound of the heterocyclic series that characterized five-membered ring structure which comprises located adjacent two nitrogen atoms and three carbon atoms. In recent years interest in the pyrazole chemistry excessively has increased due to many a wide range of properties. Because they have a wide range of specific properties such as biological activities, pharmaceutical i.e., Pyrazoles were also applied successfully in many fields; medicine, agricultural, industry, pharmaceutical chemistry so that pyrazole chemistry was quite an interesting area of research for the synthesis of their derivatives and investigates new methods. Methods: Research and online content related to synthesis pyrazole and electrophilic cyclization of molecules are reviewed. Excerpts are used to illustrate key themes about chemistry of organic substances bearing pyrazole group. All the solvents and chemical materials were purchased. All the reagents were used directly without purification. Results: The new substitute α,β-alkynic hydrazones was prepared by heating directly from thiophene-2-acetyl chloride and terminal alkyne via a palladium-catalyzed coupling reaction then a series of the new substituted pyrazole derivatives were converted via electrophilic cyclization by catalyst and characterizations of each compound were indicated by the help of spectral data. Conclusion: The new different substitute pyrazoles were synthesized via copper mediated electrophilic cyclization. Firstly, the various hydrazones derivatives were carried out by the condensation reactions of the propargyl ketone that prepared from phenyl acetylene and acyl chloride with hydrazines. The various pyrazoles contain that thiophene were obtained by electrophilic cyclization copper(I) iodide and the various hydrazones. In addition, synthesized of substitute pyrazoles may be apply the other fields because of their diverse and potent biological properties. For this reason, the syntheses of different pyrazole compounds are becoming more importance. Keywords: Alkyne, electrophilic cyclization, hydrazine, hydrazone, pyrazole.

1,2-Thiazines: One-Pot Syntheses Utilizing Mono and Diaza Analogs of Sulfones.

A one-pot Michael addition/cyclization/condensation reaction sequence for the regioselective synthesis of 1,2-thiazines, starting from propargyl ketones and NH-sulfoximines or NH-sulfondiimines, has been developed. Under mild and operationally simple reaction conditions previously unprecedented 1,2-thiazine 1-imide and 1-oxide derivatives are formed in good to excellent yields. The products represent heterocyclic building blocks, readily modifiable by a regioselective C-H bond functionalization, classical cross-coupling reactions, and deprotection.

TEMPO-catalyzed synthesis of 5-substituted isoxazoles from propargylic ketones and TMSN3

A novel and efficient TEMPO-catalyzed synthesis of 5-substituted isoxazoles from propargylic ketones and TMSN3via the radical mechanism process is described. A plausible reaction mechanism for this process is proposed.

Zinc Amide Catalyzed Regioselective Allenylation and Propargylation of Ketones with Allenyl Boronate.

Zinc amide catalyzed, regioselective allenylation and propargylation of ketones with allenyl boronate is reported. Tertiary allenyl and homopropargyl alcohols were obtained, respectively, in high selectivities, from the same starting materials, simply by changing the reaction conditions. The substrate scope was wide. Mechanistic studies suggest that the reactions are controlled under kinetic and thermodynamic conditions.

ChemInform Abstract: Application of a C—C Bond‐Forming Conjugate Addition Reaction in Asymmetric Dearomatization of β‐Naphthols.

AbstractA magnesium catalyst, generated in situ, is the active species in the title reaction which is applied to a broad spectrum of substituted naphthols and terminal propargylic ketones under conditions A).

Ruthenium‐Catalyzed Asymmetric Transfer Hydrogenation of Propargylic Ketones

AbstractThe asymmetric transfer hydrogenation of α,β‐propargyl ketones catalyzed by an in situ formed ruthenium–hydroxyamide complex was explored. The acetylenic alcohols were isolated in good to excellent yields with excellent ee values (typically >90 %) after short reaction times at room temperature.

Application of a C-C Bond-Forming Conjugate Addition Reaction in Asymmetric Dearomatization of β-Naphthols.

A C-C bond-forming conjugate reaction was successfully applied to the enantioselective dearomatization of β-naphthols. A C(sp2)-C(sp3) bond is formed by using propargylic ketones as reactive partners. Good to excellent Z/E ratios and ee values were obtained by employing an in situ generated magnesium catalyst. Further transformations of the Z-configured C-C double bond in the products were achieved under mild reaction conditions. Moreover, the stereocontrolling element of this magnesium-catalyzed dearomatization reaction was explored by computational chemistry.

Biocatalytic Asymmetric Synthesis of Optically Pure Aromatic Propargylic Amines Employing ω‐Transaminases

AbstractThe asymmetric reductive bio‐amination of prochiral aromatic propargyl ketones led to the corresponding amines in optically pure form (ee>99%). The (R)‐ as well as the (S)‐enantiomers of the propargylic amines were obtained, employing either (R)‐selective ω‐transaminases (ω‐TAs) originating from Arthrobacter sp. and Aspergillus terreus or an (S)‐selective ω‐TA from Chromobacterium violaceum. The product propargylic amines were obtained with high conversions (up to 99%). To simplify product isolation, protection of the free amino group to the corresponding acetamides or benzamides was performed without loss of optical puritiy. The final products were isolated in moderate to good yields (33–67% over two steps) in optical pure form without additional purification steps. Although propargyl ketones are described in the literature to be irreversible inhibitors for aminotransferases, suitable ω‐transaminases were identified for the amination of these compounds.magnified image

ChemInform Abstract: Copper‐Catalyzed Enantioselective Propargylic Substitution of Propargylic Acetates with Enamines.

With the use of chiral tridentate P,N,N ligand, copper-catalyzed enantioselective propargylic substitution of propargylic acetates with enamines has been achieved, giving the corresponding propargylic ketones in high yields and with excellent enantioselectivities.

Catalytic enantioselective quick route to aldol-tethered 1,6- and 1,7-enynes from ω-unsaturated aldehydes.

An effective asymmetric route to functionalized 1,6- and 1,7-enynes has been developed based on a direct cross-aldol reaction between ω-unsaturated aldehydes and propargylic aldehydes (α,β-ynals) promoted by combined α,α-dialkylprolinol ether/Brønsted acid catalysis. This synergistic activation strategy is key to accessing the corresponding aldol adducts with high stereoselectivity, both enantio- and diastereoselectivity. The aldol reaction also proceeds well with propargylic ketones (α,β-ynones) thus enabling a stereocontrolled access to the corresponding tertiary alcohols. The utility of these adducts, which are difficult to prepare through standard methodology, is demonstrated by their transformation into trisubstituted bicyclic enones using standard Pauson-Khand conditions.

Copper-catalyzed enantioselective propargylic substitution of propargylic acetates with enamines

With the use of chiral tridentate P,N,N ligand, copper-catalyzed enantioselective propargylic substitution of propargylic acetates with enamines has been achieved, giving the corresponding propargylic ketones in high yields and with excellent enantioselectivities.