Β-keto Amides Research Articles

A New Synthesis of β‐Keto Amides by Reduction of Passerini Adducts.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Ru-SYNPHOS®and Ru-DIFLUORPHOS®: Highly Efficient Catalysts for Practical Preparation of β-Hydroxy Amides

Ru-SYNPHOS® and Ru-DIFLUORPHOS® catalysts were efficiently used for the synthesis of a wide variety of chiral β-hydroxy amides via asymmetric hydrogenation of the corresponding β-keto amides.

A new synthesis of β-keto amides by reduction of Passerini adducts

The Passerini reaction between glyoxals, isocyanides and acetic acid forms β-keto acyloxyamides, which are readily transformed in β-keto amides by reductive deacetoxylation with zinc. The versatility of this procedure, which allows introducing different groups both in position-3 and the amide nitrogen, makes it ideal for its use in diversity-oriented synthesis, in combination with subsequent complexity generation reactions.

A New Regio‐ and Chemoselective Approach to β‐Keto Amides and β‐Enamino Carboxamides via 1,3,2‐Dioxaborinanes.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Lewis Acid Catalyzed Atom Transfer Radical Cyclization of Unsaturated β‐Keto Amides.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Highly Diastereoselective Synthesis of β-Hydroxy Amides from β-Keto Amides

β-Hydroxy amides with stereodefined geometry represent an important unit present in various natural products. The diastereoselective preparation of amides carrying a secondary or tertiary alcohol in β-position is described here.

Reactions of thiosemicarbazones derived from beta-keto amides and beta-keto esters with Zn(II) and Cd(II) acetates: influence of metal, substitution, reagent ratio and temperature on metal-induced cyclization.

Zinc(II) and cadmium(II) acetates were reacted in methanol under various experimental conditions with thiosemicarbazones derived from beta-keto amides or beta-keto esters (HTSC). Some of these reactions afforded thiosemicarbazonate complexes [M(TSC)2] with IR and NMR spectra compatible with N,S-coordination, but most gave complexes [ML2], where HL is a substituted 2,5-dihydro-5-oxo-1H-pyrazole-1-carbothioamide resulting from cyclization of the HTSC. Some of these pyrazolonates and two of the HL ligands were studied by X-ray diffractometry, and their structures are discussed. Surprisingly, the reactions of zinc(II) acetate with HTSC in 1:1 mol ratio usually gave a third, previously unreported type of complex with a dideprotonated ligand, [Zn(L-H)], which was also formed when [ZnL2] and Zn(OAc)2 interacted at room temperature in 1:1 mol ratio. These L-H complexes are highly insoluble in all common solvents, which hinders their characterization but suggests that they are polymeric in nature.

A New Regio- and Chemoselective Approach to β-Keto Amides and β-Enamino Carboxamides via 1,3,2-Dioxaborinanes

Surprisingly, 5,6-disubstituted 2,2-difluoro-4-alkoxy-1,3,2-dioxaborinanes, which can be easily obtained from β-keto esters, reacted regio- and chemoselectively with amines under mild reaction conditions to form 2,2-difluoro-4-alkylamino-1,3,2-dioxaborinanes in almost quantitative yields. The latter compounds can be easily deprotected, yielding β-keto amides, or directly transformed into β-enamino carboxamides. This procedure was also applied to the reaction of 2,2-difluoro-4-alkoxy-1,3,2-dioxaborinanes with arylhydrazines which selectively afforded β-hydrazono esters, in some cases without further cyclization to pyrazolones.

Highly Stereoselective Reduction of β-Keto Amides: The First General and Efficient Approach to N-mono- and non-Substitutedanti-α-Alkyl β-Hydroxy Amides

The first general protocol for the anti-selective reduction of α-alkyl-β-keto amides is described. This simple and efficient methodology based on an open-chain Felkin-Anh model pathway, allows the isolation of N-mono- andnon-substituted anti-α-substituted β-hydroxy amides in good yields and with high diastereoselectivity.

Lewis acid-catalyzed atom transfer radical cyclization of unsaturated β-keto amides

The Lewis acid-catalyzed atom transfer radical cyclization reactions of olefinic α-bromo β-keto amides were investigated. It was found Lewis acid Yb(OTf)3 or Mg(ClO4)2 not only promoted the cyclization reactions, but also resulted in excellent trans stereocontrol in the cyclization products. With the catalysis of Lewis acid Yb(OTf)3 or Mg(ClO4)2 at −78°C in the presence of Et3B/O2, the cyclization reactions of C-olefinic β-keto amides provided cyclic ketones, while the cyclization reactions of N-olefinic β-keto amides led to the formation of γ-lactams, which could be converted to 3-aza-bicyclo[3,1,0]hexan-2-ones.

Lanthanide triflate-promoted palladium-catalyzed cyclization of alkenyl beta-keto esters and amides.

[reaction: see text] Lanthanide triflates were found to promote the palladium-catalyzed cyclization of alkenyl beta-keto esters and amides. In the presence of catalytic amounts of PdCl(2)(MeCN)(2) and Ln(OTf)(3), various alkenyl beta-keto esters and amides underwent regioselective cyclization reactions to give six-, seven-, or eight-membered-ring carbocycles in moderate to excellent yields.

Manganese(III) Acetate‐Mediated Alkylation of β‐Keto Esters and β‐Keto Amides: An Enantio‐ and Diastereo‐Selective Approach to Substituted Pyrrolidinones.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Solid-phase synthesis of 3-aryl-3-oxo-propan amides by reaction of lithium enolates with 4-nitrophenyl carbamate resin or polymer-bound isocyanate

Two synthetic procedures to enable a straightforward and efficient solid-phase synthesis of 3-aryl-3-oxo-propan amides (β-keto amides) are described and compared. Lithium enolates, which can be obtained by deprotonation of methyl ketones with LiHMDS, are added to either an immobilized isocyanate or activated carbamate. After cleavage of the products from the solid support, various 3-aryl-3-oxo-propan amides are released in high yield and purity. The advantage of this method is that many of the commercially available methyl ketone building blocks can be used. The immobilized 3-aryl-3-oxo-propan amides generated may serve as intermediates for the preparation of structurally diverse libraries.

Manganese(III) acetate-mediated alkylation of beta-keto esters and beta-keto amides: an enantio- and diastereo-selective approach to substituted pyrrolidinones.

beta-Keto esters and beta-keto amides can be efficiently alkylated on reaction with enol ethers and manganese(III) acetate in the presence of copper(II) acetate. These intermolecular radical addition reactions can be used to construct quaternary carbon centres in excellent yield and this method has been utilised in a diastereoselective approach to substituted pyrrolidinones.

Parallel synthesis of 1,2,4-trisubstituted imidazoles via N-alkyl-N-(β-keto)amides using a carbazate linker

Abstract The synthesis of 1,2,4-trisubstituted imidazoles was demonstrated via the solid phase synthesis of N -alkyl- N -(β-keto)amides using a carbazate linker. The approach enabled the assembly of a diverse number of N -alkyl- N -(β-keto)amide intermediates in good yield and purity. Subsequent cyclisation in solution using NH 4 OAc led to the preparation of 1400 1,2,4-trisubstituted imidazoles.

EthylN-(3-oxobutanoyl)carbamate

The title compound, C7H11NO4, is a useful precursor in the synthesis of substituted pyrimidine bases. It is prepared from diketene and urethane and can be isolated from benzene as colorless, transparent, plate crystals. The H atom of the secondary amide forms centrosymmetric planar dimers with the carbonyl group of a second symmetry-related mol­ecule. The ketone carbonyl of the β-keto amide is present as the keto tautomer and not as the enol. The r.m.s. deviation of the atoms in the hydrogen-bonded dimer from the least-squares plane defined by those atoms is 0.014 A.

Metal-induced cyclization of thiosemicarbazones derived from beta-keto amides and beta-keto esters: open-chain and cyclized ligands in zinc(II) complexes.

The reactions of Zn(OAc)(2) with acetoacetanilide, methyl acetoacetate, o-acetoacetanisidide, and ethyl 2-methylacetoacetate thiosemicarbazones (HTSC(1), HTSC(2), HTSC(3), and HTSC(4), respectively) were explored in methanol. With HTSC(1), HTSC(2), and HTSC(3), following isolation of the corresponding zinc(II) thiosemicarbazonates [Zn(TSC(x))(2)] (x = 1, 2, 3), the mother liquors afforded pyrazolonate complexes [ZnL(1)(2)(H(2)O)] (HL(1) = 2,5-dihydro-3-methyl-5-oxo-1H-pyrazole-1-carbothioamide) that had been formed by cyclization of the corresponding TSC(-). The reaction of HTSC(4) with zinc(II) acetate gave only the pyrazolonate complex [ZnL(2)(2)(H(2)O)] (HL(2) = 2,5-dihydro-3,4-dimethyl-5-oxo-1H-pyrazole-1-carbothioamide). All compounds were studied by IR and NMR spectroscopy, and HTSC(3), [Zn(TSC(3))(2)] x DMSO, [ZnL(1)(2)(H(2)O)] x 2DMSO, and [ZnL(2)(2)(H(2)O)] x 2DMSO were also studied by X-ray diffractometry, giving a thorough picture of the cyclization process. In preliminary tests of the effects of HL(1) and [ZnL(1)(2)(H(2)O)] on rat paw inflammatory edema induced by carrageenan, HL(1) showed antiinflammatory activity.

One-pot highly stereoselective reduction of β-keto amides to syn-γ-aminols

In the presence of titanium tetrachloride, the borane/tetrahydrofuran complex can reduce 2-methyl-3-oxoamides into the corresponding syn-aminols in good yields and high diastereoselectivity. The use of borane/dimethyl sulfide instead of BH3/THF allows a partial reduction to syn-β-hydroxyamides.

Zinc carbenoid-mediated chain extension of β-keto amides

The reaction of β-keto amides with ethyl(iodomethyl)zinc provides access to a wide variety of γ-keto amides, including primary, secondary, and tertiary amides. Although the reaction of α-substituted β-keto amides are in many cases unsatisfactory, the method can be applied to a broad spectrum of substrates that possess imide and olefinic functionality.

CONVENIENT AND EFFICIENT SYNTHESES OF β-KETO ESTERS AND β-KETO AMIDES DIRECTLY FROM α-ALKYLACETYL CHLORIDES

The α-alkylacetyl chlorides were slowly treated with dried triethylamine, followed by treatment with alcohols or amines, to produce β-keto esters or β-keto amides, respectively. The process is a convenient alternative to prepare β-keto esters and β-keto amides.