Enantioselective formal synthesis of tridemethylisovelleral

A simple and efficient synthetic route to the bicyclic α,β-unsaturated β-keto ester methyl (3aS,7aS)-6-oxo-2,3,3a,6,7,7a-hexahydro-1H-indene-5-carboxylate, a versatile intermediate in the synthesis of biologically active unsaturated 1,4-dialdehydes, is described. The synthesis includes a chirality introducing nonenzymatic asymmetric desymmetrization (ADS) reaction of a cyclic meso-anhydride 4 and a modified Hofmann method for preparing exocyclic dienes. The ester was synthesized in a moderate overall yield (19%) from 6 and with an excellent enantioselectivity (>90%).     

Enantioselective α-hydroxylation of β-keto esters catalyzed by chiral S-timolol derivatives

A screen of aryloxy aminopropanol organocatalysts derived from the β-blocker inhibitor S-timolol determined the most active catalyst of asymmetric α-hydroxylation of β-keto esters. (R)-1-(tert-butylamino)-3-(3,4,5-trimethoxyphenoxy) propan-2-ol (3k) was the most effective derivative, enantioselectively catalyzing α-hydroxylation of β-keto esters using tert-butyl hydroperoxide as the oxidant in hexane to afford the corresponding products in excellent yield and with good enantioselectivity (up to 96% yield, 88% ee).     

Enantio- and diastereoselective synthesis of 4′-α-substituted carbocyclic nucleosides

Enantio- and diastereoselective synthesis of 4-α-alkylcarbovir derivatives 5 were achieved based on Sakai's asymmetric alkylation of β-keto esters. The key carbocyclic intermediate 14 was synthesized from 8 via an eleven-step sequence. Coupling of 14 with 2-amino-6-chloropurine followed by desilylation and subsequent hydrolysis gave the target compounds 5 in moderate yields.     

A highly enantioselective [4+2] cycloaddition involving aldehydes and β,γ-unsaturated-α-keto esters

A stereoselective inverse electron demand oxo-Diels-Alder reaction involving electron poor dienes (γ-aryl-β,γ-unsaturated-α-keto ester) and electron rich dienophiles has been studied. These cycloaddition reactions are extremely useful for the construction of O-, N-, S-centered heterocyclic compounds, which are routinely used in both synthetic organic and medicinal chemistry. The [4+2] hetero cycloaddition reactions involving various aldehydes and β,γ-unsaturated-α-keto esters were carried out in which three different types of substituted proline catalysts were examined. For these reactions, high selectivities (enantiomeric excess 93–98%) were obtained using catalyst 3. Due to the bulkiness of catalyst 3, compared to the other catalysts tested, it is more efficient at catalyzing these type reactions.     

One-pot synthesis of highly substituted pyrroles using nano copper oxide as an effective heterogeneous nanocatalyst

A convenient one-pot four-component reaction of aromatic aldehydes, β-keto esters and nitromethane in the presence an amine and 10 mol% CuO nanoparticles for the synthesis of highly substituted pyrroles is described. Excellent yields, easily available and less expensive catalyst and easy work-up are the key features of the present method. The NMR spectrum was coupled with quantum chemical calculations in DFT approach using the hybrid B3LYP exchange-correlation functional to confirm the structures of (1-benzyl-4-(4-chlorophenyl)-2-methyl-1H-pyrrol-3-yl)(phenyl)methanone 14 and 1-(1-benzyl-4-(4-chlorophenyl)-2-phenyl-1H-pyrrol-3-yl)ethanone 14′.     

Stereoselective synthesis of the C31-C39 unit of (+)-phorboxazoles from m-anisaldehyde

A stereoselective route for the synthesis of the C31-C39 fragment of (+)-phorboxazoles is described. The route features Birch reduction, ozonolysis and acid-catalysed cyclisation of enantiopure precursors as key transformations to give the tetrahydropyran ring, starting from m-anisaldehyde as a masked β-keto ester to obtain the pyran skeleton of compound 1.     

Efficient trans-acetoacylation mediated by ytterbium(III) triflate as a catalyst under solvent-free condition

A simple and efficient trans-acetoacylation method for the synthesis of β-keto ester derivatives has been described using ytterbium(III) triflate as a new catalyst under solvent-free condition. This method was found to be efficient and convenient for the synthesis of a wide variety of β-keto ester derivatives.     

Visible light mediated photocatalytic oxidative coupling reaction of N-phenyl tetrahydroisoquinoline with β-keto acids

A visible light mediated photocatalytic oxidative coupling reaction of N-phenyl tetrahydroisoquinoline with β-keto acids has been developed. This approach provides a mild and operationally simple access to the synthesis of C1-acylmethylated tetrahydroisoquinolines.     

Quinoxaline synthesis in novel tandem one-pot protocol

A variety of quinoxalines were synthesized via tandem one-pot procedure for the first time in water medium. The key strategy was the in situ preparation of α-halo-β-keto esters by the reaction of N-bromo succinimide with β-keto esters and further condensation with phenylene diamines. This novel eco-friendly approach offers an easy, efficient, and mild synthesis of highly substituted quinoxalines in good yields.     

A new method for the synthesis of N-protected β-amino-α-keto esters from fluoroalkanesulfonylazides and α-keto esters

In the presence of a secondary amine, treatment of α-keto esters with fluoroalkanesulfonyl azides at room temperature afforded N-sulfonyl protected β-amino-α-keto esters in good to excellent yields. This reaction provided a novel, direct and convenient access to N-sulfonyl protected β-amino-α-keto esters from α-keto esters and fluoroalkanesulfonyl azides under mild conditions. However, the reaction of fluoroalkanesulfonyl azides with β-ketoester enamines afforded two products: N-fluoroalkanesulfonyl amidines and diazoacetate. The reaction mechanism is discussed.     

Simultaneous Ring-Opened THF and insertion of diazoketone derived carbene into carbonyl O-H: Synthesis for β-keto enol ethers

A novel tandem synthesis of β-keto enol ethers was developed via the reaction of α-diazoketones, 1,3-diketones and THF catalyzed by cheap and available CuI under extremely simple conditions. During the course of the reaction, the ring-opened THF and diazocarbonyl derived carbene simultaneously inserted into O-H of 1,3-diketones.     

Diastereoselectivity in the Carroll rearrangement of β-keto esters of tertiary allylic alcohols

Carroll rearrangement of β-keto esters derived from tertiary allylic alcohols, for example, 7, under basic conditions followed by decarboxylation of the resulting β-keto acids yielded the expected γ,δ-unsaturated methyl ketones 8 with a range of olefin geometries from 100:0 to 1:1.8 E/Z, depending on the relative steric requirements of the two groups at the allylic center.     

Phthalimide-N-sulfenyl chloride in the Ti-catalyzed asymmetric sulfenylation of β-keto esters

The enantioselective sulfenylation of β-keto esters was carried out using phthalimide-N-sulfenyl chloride in the presence of a Ti(TADDOLato) catalyst affording up to 60% ee. X-ray crystal structures of product compounds 3a and 9a were determined.     

Aminolysis of 2,2-difluoro-4-alkoxy-1,3,2-dioxaborinanes: route to β-keto amides and β-enamino carboxamides

4-Alkoxy substituted 1,3,2-dioxaborinanes 1, readily available from β-keto esters, undergo substitution reactions under mild reaction conditions with primary and secondary amines, deriving the 4-alkylamino analogue 2. Reactions of 1 with substituted phenylhydrazines gave the corresponding hydrazones, or pyrazolones, and 5-alkoxy-1H-pyrazoles as a mixture of products.     

Cu(I)-catalyzed reaction of diazo compounds with terminal alkynes: a direct synthesis of trisubstituted furans

A method for the synthesis of tri-substituted furans has been developed based on Cu(I)-catalyzed reaction of terminal alkynes with β-keto α-diazoesters. This method for the synthesis of 2,3,5-trisubstituted furans is operationally simple and applicable to wide substrate scope. Moreover, this synthesis employs cheap Cu(MeCN)₄PF₆ as the catalyst and no additional ligand is needed. Similar reaction has also been applied to ethyl (E)-2-diazo-3-(methoxyimino)butanoate for the synthesis of 2,3,5-trisubstituted N-methoxypyrroles with limited success.     

Oxidative bromination of ketones using ammonium bromide and oxone®

A highly efficient, environmentally safe and economic method for selective α-monobromination of aralkyl, cyclic, acyclic, 1,3-diketones and β-keto esters and α,α-dibromination of 1,3-diketones and β-keto esters without catalyst is reported using ammonium bromide as a bromine source and oxone® as an oxidant. The reaction proceeds at ambient temperature and yields range from moderate to excellent. Bromination of unsymmetrical ketones takes place at the less substituted α-position predominantly. Aromatisation of tetralones is also carried out with this reagent system.     

Total synthesis of monocyclic β-lactam antibiotics,nocardicin A and D

The total synthesis of monocyclic β-lactam antibiotics, nocardicins A (1a) and D (1d), is described. 3-Aminonocardicinic acid (3-ANA, 2) was synthesized from p-hydroxyphenylglycine via an acid chloride-imine cyloaddition reaction. The side chain amino acid 13 was prepared via a key step of condensation of p-hydroxyacetophenone and α-phthalimidobutyrolactone. Acylation of 3-ANA with 13 gave nocardicin D, from which nocardicin A was obtained by oximation.     

A versatile and efficient synthesis of (2S)-2-(hydroxymethyl)-N-Boc-2,3-dihydro-4-pyridone

A versatile and efficient method for the preparation of (2S)-2-(hydroxymethyl)-N-Boc-2,3-dihydro-4-pyridone from l-(−)-phenylalanine 2 utilising the aromatic system as a masked β-keto aldehyde was developed. The key step in the sequence is an intramolecular cyclisation of 6 to give 2,3-dihydropyridin-4-ones.     

Cu(I)-catalyzed asymmetric α-hydroxylation of β-keto esters in the presence of chiral phosphine-Schiff base-type ligands

Chiral phosphine-Schiff base-type ligand L1 prepared from (R)-(?)-2-(diphenylphosphino)-1,1′-binaphthyl-2′-amine was found to be a fairly effective ligand for Cu(I)-promoted enantioselective α-hydroxylation of β-keto esters using oxaziridine 2a as the oxidant to give the corresponding products in high yields along with moderate enantioselectivities.