Recyclable polymeric pi-acid catalyst effective on Mannich-type reaction in water

Polymer-supported dicyanoketene acetal (poly-DCKA-1), synthesized by copolymerization of a DCKA bearing a 4-vinylbenzyl group with ethyleneglycol dimethacrylate, was found to be an excellent recyclable catalyst for the three-component Mannich-type reaction of aldehydes, aromatic amines, and TMS enolate of ethyl isobutyrate in water as the sole solvent.     

A direct catalytic asymmetric Mannich-type reaction via a dinuclear zinc catalyst: synthesis of either anti- or syn-alpha-hydroxy-beta-amino ketones

The use of imines bearing a hydrolyzable nitrogen substituent in direct asymmetric Mannich reactions with alpha-hydroxyketones is developed. Previous work focused on the use of N-arylimines or nonenolizable imines, and the latter with only methoxy-substituted alpha-hydroxyacetophenones. Using a dinuclear catalyst devised from 2,6-di-(S)-2'-diphenylhydroxymethylpyrrolidino-N-methyl)-4-methylphenol and diethylzinc, a broad array of hydroxyacetylated aromatics, including phenyl, 2-furyl, 1-naphthyl, and 2-naphthyl, react well. In addition, the reactions focused on the use of enolizable imines. With the N-diphenylphosphinoyl, the reactions are anti selective with enantiomeric excesses ranging from 83 to 99%, except for the reaction of the 2-methoxy-2'-hydroxyacetylbenzene. With the N-Boc-imines, the reactions were syn selective with enantiomeric excesses from 90 to 94%. The dependence of the diastereoselectivity on the nature of the N-substituent presumably arises from the steric demands of the diphenylphosphinoyl group.     

Facile and diastereoselective synthesis of β-acetamido ketones and keto esters via direct Mannich-type reaction

A Mannich-type three-component reaction involving aldehydes, acetamide, and enolizable ketones or β-keto esters for the preparation of β-acetamido carbonyl compounds in the presence of TMSCl is described. This newly developed protocol is operationally convenient, widely applicable, and highly diastereoselective.     

Chiral tetraaminophosphonium carboxylate-catalyzed direct Mannich-type reaction

The cooperative asymmetric catalysis of chiral tetraaminophosphonium carboxylate (P,S)-1.OCOR has been established, and its synthetic utility has been successfully demonstrated by application to the highly enantioselective direct Mannich-type reaction of azlactones with N-sulfonyl imines. The present study stimulates the cultivation of the potential of the chiral quaternary onium salt catalysis by the structural modification of organic anion.     

Stereoselective synthesis of β-amino ketones via direct Mannich-type reaction catalyzed with silica sulfuric acid

At room temperature, the direct Mannich-type reaction of a variety of in situ generated aldimines using aldehydes and anilines with ketones in a three-component reaction was efficiently catalyzed by silica sulfuric acid (SSA) in EtOH. This rapid reaction afforded the corresponding β-amino ketones in good yields with excellent stereoselectivities and catalyst was recyclable.     

HClO4-SiO2 catalyzed stereoselective synthesis of β-amino ketones via a direct Mannich-type reaction

The HClO₄-SiO₂ catalyzed three-component, one-pot Mannich reaction of ketones, aromatic aldehydes and aromatic amines is carried out in ethanol to afford the corresponding β-amino ketones in good yields and high stereoselectivities in favor of the anti-isomer. Three new compounds are reported.     

anti-Selective direct catalytic asymmetric Mannich-type reaction of hydroxyketone providing beta-amino alcohols

An anti-selective direct catalytic asymmetric Mannich-type reaction is described. The Et(2)Zn/(S,S)-linked-BINOL 1 = 4/1 complex promoted a Mannich-type reaction of 2-hydroxy-2'-methoxyacetophenone (2) and N-diphenylphosphinoyl imines 3. Using as little as 0.25-1 mol % of the catalyst, we obtained Mannich adducts 4 in excellent yield (up to 99%), diastereoselectivity (anti/syn = up to >98/2), and enantiomeric excess (up to >99.5%). The anti-selectivity in the present system is complementary to that observed using previously reported methods, providing a novel efficient method to synthesize anti-beta-amino alcohols in a highly enantioselective manner. Facile deprotection of the N-diphenylphosphinoyl group and commercial availability of both Et(2)Zn solution and (S,S)-linked-BINOL 1 also make the present catalysis practical.     

Catalytic Mannich-type reaction of phosphorylimidates

Phosphorylimidates reacted with N-Boc imines in the presence of a catalytic amount of potassium hexamethyldisilazide, to afford the corresponding Mannich-type adducts in high yields. It was shown that, like sulfonylimidates, phosphorylimidates can function as ester equivalents. In contrast to sulfonylimidates however, phosphorylimidates exhibited high anti-selectivity even in low polar solvents. An explanation for the anti-selectivity is given.     

Synthesis of cyclic enones via direct palladium-catalyzed aerobic dehydrogenation of ketones

α,β-Unsaturated carbonyl compounds are versatile intermediates in the synthesis of pharmaceuticals and biologically active compounds. Here, we report the discovery and application of Pd(DMSO)(2)(TFA)(2) as a catalyst for direct dehydrogenation of cyclohexanones and other cyclic ketones to the corresponding enones, using O(2) as the oxidant. The substrate scope includes heterocyclic ketones and several natural-product precursors.     

Development of a convoluted polymeric nanopalladium catalyst: α-alkylation of ketones and ring-opening alkylation of cyclic 1,3-diketones with primary alcohols

A novel solid-phase catalyst of palladium nanoparticles, nano-Pd-V, was prepared from PdCl₂ with main-chain viologen polymers via complexation and reduction. This insoluble nanocatalyst nano-Pd-V efficiently promoted α-alkylation of ketones with primary alcohols in the presence of Ba(OH)₂·H₂O under atmospheric conditions without organic solvents. The nano-Pd-V catalyst was reused without loss of catalytic activity. Ring-opening alkylation of cyclic 1,3-diketones with primary alcohols was also catalyzed by the nano-Pd-V catalyst.     

Asymmetric hydrogenation of aromatic ketones using polymeric catalyst prepared from polymer-supported 1,2-diamine

tert-Butyloxycarbonyl (Boc) protected chiral 1,2-diamine monomers 3 were copolymerized with achiral vinyl monomers such as styrene, methacrylates, acrylates, methacrylamide, and acrylamide to give crosslinked polymers P2 containing chiral 1,2-diamine moieties. Deprotection of the Boc groups in the polymer afforded the crosslinked chiral 1,2-diamine polymer P3. The diamine polymer was allowed to react with RuCl₂/BINAP in DMF to form polymeric complex. Asymmetric hydrogenation of aromatic ketones smoothly proceeded using the polymeric complex to give the corresponding secondary alcohol in quantitative yield with high level of enantioselectivity up to 98% ee in a mixed solvent of DMF and 2-propanol. The polymeric catalyst can be recycled several times without loss of the activity.     

Beyond the corey reaction: one-step diolefination of cyclic ketones

The reactivities of the cyclic ketones cycloheptanone, cyclodecanone, and cycloundecanone with dimethylsulfoxonium methylide generated from trimethylsulfoxonium iodide and base (NaH) were studied in diglyme at 130 degrees C. Oxiranes, which primarily form via the Corey reaction, lead to ring expansions to give oxetanes and oxacyclopentanes when an excess of dimethylsulfoxonium methylide is used. The Corey reaction is suppressed in the presence of excess of base, and 1,3-terminal dienes form instead (we term this reaction the Yurchenko diolefination). Our mechanistic proposal involves the deprotonation of the betaine that forms after the attack of dimethylsulfoxonium methylide on the carbonyl group of the ketone. The key step of the diolefination reaction involves a [2,3]-sigmatropic rearrangement of the ylide to a gamma-unsaturated sulfoxide with a barrier of 9.9 kcal/mol (DeltaH298, MP2/cc-pVDZ, for the cycloheptane derivative). The elimination of sulfenic acid from the gamma-unsaturated sulfoxide in the terminal step of the diolefination is associated with a higher barrier (17.3 kcal/mol) but is strongly accelerated in the presence of base. The reactivity of cyclic ketones in the Yurchenko reaction depends on the ring size; medium-sized cyclodecanone is less reactive than either cycloheptanone or cyclododecanone.     

Asymmetric direct aldol reaction of 1,2-diketones and ketones mediated by proline derivatives

The direct aldol reaction of 1,2-diketones and ketones mediated by proline derivatives yields the corresponding 2-hydroxy 1,4-diketones in high regioselectivity, diastereoselectivity and good enantioselectivity. This reaction provides an easy access to optically active tertiary alcohols, which are flanked by two carbonyl groups for further elaborations.     

Chiral ammonium betaines: a bifunctional organic base catalyst for asymmetric Mannich-type reaction of alpha-nitrocarboxylates

A chiral ammonium betaine, an intramolecular ion-pairing quaternary ammonium aryloxide 3, has been designed and its vast potential as an enantioselective organic base catalyst has been successfully demonstrated in the highly enantioselective direct Mannich-type reaction of alpha-substituted alpha-nitrocarboxylates 2 with various N-Boc imines 1. The present study provides a conceptually new approach toward the design of bifunctional, chiral quaternary ammonium salts and their utilizations as a homogeneous organic molecular catalyst.     

Preparation of ketones by direct reaction of grignard reagents with acid chlorides in tetrahydrofuran

Grignard reagents react with acid chlorides in tetrahydrofuran at low temperature to produce ketones in excellent yields. The results reported here strongly indicate the importance of the solvent in Grignard reagent chemistry.     

Asymmetric direct aldol reaction of functionalized ketones catalyzed by amine organocatalysts based on bispidine

Organocatalysts containing primary-secondary amine based on bispidine and amino acid have been designed to catalyze the asymmetric direct aldol reaction of functionalized ketones including alpha-keto phosphonates, alpha-keto esters, as well as alpha,alpha-dialkoxy ketones as aldol reaction acceptors. The corresponding products with chiral tertiary alcohols were obtained in moderate to high yields (up to 97%) and high enantioselectivities (up to 98% ee). A theoretical study of transition structures demonstrated that protonated piperidine was important for the reactivity and enantioselectivity of this reaction.     

Highly enantioselective direct conjugate addition of ketones to nitroalkenes promoted by a chiral primary amine-thiourea catalyst

Primary amine-thiourea derivative 1 is an active and highly enantioselective catalyst for the conjugate addition of ketones to nitroalkenes. Broad substrate scope is described, with nitroalkenes bearing either aromatic or aliphatic substituents and a wide variety of ketones shown to be useful reacting partners. Ethyl ketones react preferentially, generating anti products with methyl-bearing stereocenters with good-to-excellent diastereoselectivity. An enamine mechanism is indicated, with cooperative activation of the electrophile by the thiourea and of the ketone by the primary amine.     

One-pot three-component Mannich-type reaction catalyzed by trifluoromethanesulfonic acid in water

One-pot three-component Mannich-type reaction of ketones, aldehydes and amines was efficiently catalyzed by liquid trifluoromethanesulfonic acid in water at ambient temperature. The high yield of corresponding β-amino ketones compounds were achieved. The proposed method is mild, green, simple and efficient.     

Proline-catalyzed direct asymmetric aldol reaction of trifluoroacetaldehyde ethyl hemiacetal with ketones

l-Proline-catalyzed direct asymmetric aldol reaction of trifluoroacetaldehyde ethyl hemiacetal with unmodified ketones smoothly occurred at ambient temperature to produce β-hydroxy-β-trifluoromethylated ketones with good to excellent diastereo (up to 96% de) and enantioselectivities (up to 91% ee).