I2/CuO-catalyzed tandem cyclization strategy for one-pot synthesis of substituted 2-aminothiozole from easily available aromatic ketones/α,β-unsaturated ketones and thiourea

A concise and efficient one-pot process from easily available methyl ketones/unsaturated methyl ketones and thiourea was developed for the synthesis of 2-aminothiazoles under the media of I₂/CuO. The method can highly stereoselectivity obtain the E-isomers of 4-ethenyl-2-aminothiazoles (5a–f). All these target molecules were characterized by NMR, HRMS and IR spectra. Furthermore, the target compounds 3c and 5b were further determined by X-ray crystallographic analysis.     

Hydrogen bond catalyzed direct reductive amination of ketones

[reaction: see text] A novel, biomimetic concept for the direct reductive amination of ketones is described that relies on selective imine activation by hydrogen bond formation. The mild, acid- and metal-free process requires only catalytic amounts of thiourea as hydrogen bond donor and utilizes the Hantzsch ester for transfer hydrogenation. The method allows the efficient synthesis of structurally diverse amines.     

Asymmetric synthesis of α-alkyl α-selenocarbonyl compounds catalyzed by bifunctional organocatalysts

A new organocatalytic approach for the synthesis of a variety of α-alkyl, α-phenylselenyl ketones as well as their corresponding esters and amides, by the addition of α-selenocarbonyl derivatives to nitroalkenes catalyzed by thiourea or squaramide cinchona catalysts, is presented. This catalytic system allows the preparation in high yields of enantiomerically enriched selenocarbonyl derivatives bearing two chiral centers with excellent ee's and dr's by using catalytic loadings of 3 mol%.     

Synthesis of hindered tertiary amines by a mild reductive amination procedure

An efficient metal-free procedure for the synthesis of tertiary amines by the reductive amination of carbonyl compounds is reported, which allows a convergent access to sterically hindered amines of the general formulas NR(R′)₂ and NRR′R″. The mild and operationally simple protocol uses the Hantzsch ester for transfer hydrogenation and catalytic amounts of thiourea for imine activation.     

Synthesis of pyridyl- and quinolyl-substituted 2-aminothiazoles

Five 2-amino-4-(x-pyridyl)- and 2-amino-4-(x-quinolyl)thiazoles have been synthesized by the condensation of thiourea with bromoacetylpyridines and -quinolines. The reaction of pyridyl pyridylmethyl ketones with thiourea and halogens produced four 2-aminothiazoles possessing pyridyl substituents in 4- and 5-positions on the thiazole ring. Treatment of N-(3-pyridyl)- and N-(3-quinoiyl)thiourea with α-bromoketones gave seven new 2-(3-pyridyl)amino- and 2-(3-quinolyl)aminothiazoles. The ultraviolet spectra of the pyridyl- and quinolyl- substituted 2-aminothiazoles were recorded.     

Montmorillonite K10: an effective catalyst for synthesis of 2-aminothiazoles

Research on Chemical Intermediates - An efficient one-pot synthesis of 2-aminothiazoles from methylcarbonyl and thiourea has been developed using montmorillonite-K10 as a catalyst at...     

Organocatalytic asymmetric transferhydrogenation of beta-nitroacrylates: accessing beta2-amino acids

We describe a highly efficient and enantioselective Hantzsch ester mediated conjugate reduction of beta-nitroacrylates that is catalyzed by a Jacobsen thiourea catalyst as a key step in a new route to optically active beta2-amino acids.     

Kinetic Resolution of β‐Sulfonyl Ketones through Enantioselective β‐Elimination using a Cation‐Binding Polyether Catalyst

Reported herein is the first enantioselective β‐elimination reaction catalyzed by a chiral cation‐binding polyether. By using this catalytic protocol, a wide range of β‐sulfonyl ketones could be effectively resolved with high stereoselectivity (S up to >300). Key to the success of this process is the favorable secondary interactions of the catalyst with the Lewis basic groups on the sulfone substrate. The enone product of this process can be easily converted into the racemic starting material, and allows an effective recycling and overall synthesis of chiral β‐sulfonyl ketones in high yield and excellent enantioselectivity.     

Studies towards iodine-catalyzed dehydrative-cycloisomerization of pent-4-yne-1,2-diols to di- and tri-substituted furans

An efficient and single-step iodine catalyzed and metal-free synthesis of di and tri-substituted 2-methylfuran derivatives were achieved from 1-popargyl-1,2-diols. Stereospecific synthesis of starting 1,2-diols was achieved by indium mediated Barbier type propargylation on corresponding keto-alcohols or by sodium borohydride mediated reduction of 2-hydroxy-2-propargyl ketones. The furan synthesis proceeded through iodine mediated 5-exo-trig cyclization, dehydration and reductive deiodination. The method was applied to the synthesis of 2-methylfuran fused to phenanthrene, pyrene and acenaphthylene rings.     

Citric Acid‐catalyzed Synthesis of 2,4‐Disubstituted Thiazoles from Ketones via C–Br,C–S,and C–N Bond Formations in One Pot: A Green Approach

An improved and greener protocol has been developed for the synthesis of 2,4‐disubstituted thiazoles via C–Br, C–S, and, C–N bond formations in a single step from readily available ketones, N‐bromosuccinimide (NBS), and thiourea catalyzed by citric acid in a mixture of ethanol and water (3:1) under reflux conditions. This method has the advantages of freedom from the isolation of lachrymatory α‐bromoketones, ease of carrying out, cleaner reaction profile, broad substrate scope, freedom from chromatographic purification, and suitability for large‐scale synthesis.     

Novel one step synthesis of imidazo[1,2-a]pyridines and Zolimidine via iron/iodine-catalyzed Ortoleva-King type protocol

Imidazo[1,2-a]pyridines form versatile scaffolds in pharmaceutical industry arising from their diverse biological activities. The synthesis of these molecules thus has been of great interest and resulted in the development of a large number of new methodologies. Herein we describe the first iron-catalyzed Ortoleva-King type protocol towards the synthesis of these fused heterocyclic compounds. This methodology employs cheap and easily available FeCl₃·6H₂O and molecular iodine as the catalytic system. The procedure has been well explored by extending the substrate scope with a variety of aromatic ketones and 2-aminopyridines to furnish different imidazo[1,2-a]pyridine derivatives in moderate to good yields. A successful application of this protocol was also demonstrated by achieving direct one step synthesis of the gastro protective drug, Zolimidine.     

Novel α-tosyloxylation of ketones catalyzed by the in situ generated hypoiodous acid from alkyl iodide

Using a catalytic amount of 1-iodopropane, a novel and efficient procedure has been developed for direct preparation of α-tosyloxyketones from ketones. In this protocol, 1-iodopropane is first oxidized into iodosylpropane, which decomposes to form the key catalyst hypoiodous acid. With this method, not only α-tosyloxyketones, but also other α-sulfonyloxyketones have been prepared in moderate to good yields, which extends the application of alkyl substituted hypervalent iodine reagents in organic synthesis.     

Migratory Hydrogenation of Terminal Alkynes by Base/Cobalt Relay Catalysis

Migratory functionalization of alkenes has emerged as a powerful strategy to achieve functionalization at a distal position to the original reactive site on a hydrocarbon chain. However, an analogous protocol for alkyne substrates is yet to be developed. Herein, a base and cobalt relay catalytic process for the selective synthesis of (Z)‐2‐alkenes and conjugated E alkenes by migratory hydrogenation of terminal alkynes is disclosed. Mechanistic studies support a relay catalytic process involving a sequential base‐catalyzed isomerization of terminal alkynes and cobalt‐catalyzed hydrogenation of either 2‐alkynes or conjugated diene intermediates. Notably, this practical non‐noble metal catalytic system enables efficient control of the chemo‐, regio‐, and stereoselectivity of this transformation.     

Microwave promoted synthesis of functionalized 2-aminothiazoles

Microwave irradiation promotes the rapid one-pot synthesis of 2-aminothiazoles fromed via the condensation of α-bromoketones with thiourea.     

Convenient and simple synthesis of 2-aminothiazoles by the reaction of α-halo ketone carbonyls with ammonium thiocyanate in the presence of N-methylimidazole

Substituted 2-aminothiazole derivatives were obtained as a result of N-methylimidazole catalyzed cyclization of α-halo ketone carbonyls with ammonium thiocyanate in water-alcoholic media. The generality of the method has been demonstrated by screening a series of aromatic/heteroaromatic/aliphatic α-halo ketones, α-halo β-diketones, and α-halo β-ketoesters. The developed method is simple, mild, and general route for the preparation of diversely functionalized 2-aminothiazoles in good to moderate yields from readily available starting materials.     

Hydrogenation of olefins using Hantzsch ester catalyzed by palladium on carbon

Hantzsch 1,4-dihydropyridine (HEH), a well-known model compound of coenzyme NAD(P)H was found as an efficient reducing agent in hydrogenation of unactivated olefins catalyzed by Pd/C. α,β-Unsaturated ketones also underwent hydrogenation, affording the corresponding saturated ketones selectively.     

Remarkable Differences in Reactivity between Benzothiazoline and Hantzsch Ester as a Hydrogen Donor in Chiral Phosphoric Acid Catalyzed Asymmetric Reductive Amination of Ketones

Described herein are differences in behavior between a Hantzsch ester and a benzothiazoline as hydrogen donors in the chiral phosphoric acid catalyzed asymmetric reductive amination of ketones with p‐anisidine. The asymmetric reductive amination of ketones with a Hantzsch ester as a hydrogen donor provided the corresponding chiral amines exclusively, regardless of the structures of the ketones, whereas a similar transformation with a benzothiazoline provided chiral amines and p‐methoxyphenyl‐protected primary amines in variable yields, depending on the structures of both the ketones and benzothiazolines. Because a benzothiazoline has an N,S‐acetal moiety that is vulnerable to p‐anisidine, the primary amine can be formed through transimination of the benzothiazoline with p‐anisidine followed by reduction of the resulting aldimine with remaining benzothiazoline.     

Indole Synthesis by Conjugate Addition of Anilines to Activated Acetylenes and an Unusual Ligand‐Free Copper(II)‐Mediated Intramolecular Cross‐Coupling

A versatile new synthesis of indoles was achieved by the conjugate addition of N‐formyl‐2‐haloanilines to acetylenic sulfones, ketones, and esters followed by a copper‐catalyzed intramolecular C‐arylation. The conjugate addition step was conducted under exceptionally mild conditions at room temperature in basic, aqueous DMF. Surprisingly, the C‐arylation was performed most effectively by employing copper(II) acetate as the catalyst in the absence of external ligands, without the need for protection from air or water. An unusual feature of this process, for the case of acetylenic ketones, is the ability of the initial conjugate‐addition product to serve as a ligand for the catalyst, which enables it to participate in the catalysis of its further transformation to the final indole product. Mechanistic studies, including EPR experiments, indicated that copper(II) is reduced to the active copper(I) species by the formate ion that is produced by the base‐catalyzed hydrolysis of DMF. This process also served to recycle any copper(II) that was produced by the adventitious oxidation of copper(I), thereby preventing deactivation of the catalyst. Several examples of reactions involving acetylenic sulfones attached to a modified Merrifield resin demonstrated the feasibility of solid‐phase synthesis of indoles by using this protocol, and tricyclic products were obtained in one pot by employing acetylenic sulfones that contain chloroalkyl substituents.     

Access to All‐Carbon Spirocycles through a Carbene and Thiourea Cocatalytic Desymmetrization Cascade Reaction

A new catalytic approach for rapid asymmetric access to spirocycles is disclosed. The reaction involves a carbene‐ and thiourea‐cocatalyzed desymmetrization process with the simultaneous installation of a spirocyclic core. The use of a thiourea cocatalyst is critical to turn on this reaction, as no product was formed in the absence of a thiourea. Our study constitutes the first success in the carbene‐catalyzed enantioselective synthesis of all‐carbon spirocycles. The reaction products can be readily transformed into sophisticated multicyclic molecules and chiral ligands.     

Catalytic asymmetric cyanosilylation of ketones with chiral Lewis base

The development of broadly applicable and practical catalytic approaches for the enantioselective creation of quaternary stereocenters remains a highly desirable yet challenging goal. In this Communication, we describe a highly enantioselective cyanosilylation of acetal ketones (alpha,alpha-dialkoxy ketones) catalyzed by modified cinchona alkaloids. This reaction is the first highly enantioselective cyanosilylation of ketones catalyzed by an organic chiral Lewis base and is found to be highly efficient with acetal ketones bearing a broad range of alkyl, aryl, alkenyl, and alkynyl substituents. This new catalytic asymmetric reaction, coupled with the versatility of the acetal functionality, provides a broadly useful synthetic method for chiral building blocks bearing quaternary stereocenters. Acetal ketones, readily accessible but previously unexplored in asymmetric synthesis, demonstrate unusual reactivity and selectivity toward the nucleophilic cyanosilylation, thereby suggesting that they may be interesting substrates for other catalytic enantioselective reactions.