Reductive pinacol-type rearrangement of chiral α-mesyloxy ketones promoted by organoaluminum compounds

Reductive pinacol-type rearrangement of chiral α-mesyloxy ketones was effected by organoaluminums (DIBAL in combination with Et₃Al or Et₂AlCl) leading to enantiomerically pure 2-aryl- or 2-alkenyl-1-propanols.     

Rhodium-catalyzed direct aldol condensation of ketones: a facile synthesis of fused aromatic compounds

Cationic rhodium complex [Cp^∗Rh(η⁶-C₆H₆)](BF₄)₂ (1) acts as an efficient catalyst for direct aldol condensation of ketones. The method can be applied to one-pot synthesis of fused aromatic compounds from cyclic ketones via sequential C-C bond formations.     

A new protocol for a regioselective aldol condensation as an alternative convenient synthesis of beta-ketols and alpha,beta-unsaturated ketones

A general and convenient synthesis of beta-ketols and alpha,beta-alkenones has been achieved by a Knoevenagel condensation of a beta-ketoacid with an aldehyde in aqueous medium. Saponification of a beta-ketoester by an aqueous KOH 10% solution gives the potassium salt of the beta-ketoacid, which is condensed in situ with an aldehyde at pH 7.8-8.0, at 60 degrees C for 5-6 h. The intermediate beta-ketocarboxylate is smoothly decarboxylated in the reaction medium, giving the beta-ketol in high yield (75-90%). Acidification of the reaction mixture at pH 1 and heating at 70 degrees C under vigorous stirring for 6 h, leads directly to the corresponding alpha,beta-unsaturated ketone in good yield (65-75%).     

Regioselectivity in the cross condensation of α,β-unsaturated aldehydes and methyl ketones promoted by magnesium phenoxides

“Kinetic selectivity” in the cross condensation of α,β-unsaturated aldehydes and methyl ketones are obtained using 2,4,6-trimethylphenoxymagnesium bromide (2,4,6-TMPOMgBr) in benzene as catalyst.     

Regiospecific organocatalytic asymmetric aldol reaction of methyl ketones and alpha,beta-unsaturated trifluoromethyl ketones

[structure: see text]. The aldol reaction of methyl ketones and alpha,beta-unsaturated trifluoromethyl ketones occurred under mild conditions with the combination of proline-derived N-sulfonylamide and trifluoroacetic acid as the catalyst to give the corresponding unsaturated alpha-trifluoromethyl tertiary alcohols in high yields with good enatioselectivities.     

The synthesis of unsaturated trifluoromethyl ketones by regioselective organocuprate addition to acetylemic trifluoromethyl ketones

Regiospecific and stereoselective synthesis of unsaturated trifluoromethyl ketones has been accomplished by the addition of higher order cyano cuprates to acetylenic trifluoromethyl ketones.     

Generation of rhodium enolates via retro-aldol reaction and its application to regioselective aldol reaction

Retro-aldol reactions of β-hydroxy ketones take place under rhodium catalysis, leading to regioselective formation of the corresponding rhodium enolates. The enolates react with aldehydes in situ to afford the corresponding aldol adducts in high yields.     

Stereoselective aldol coupling of α,β-acetylenic ketones promoted by MgI2

A highly stereoselective synthesis of (Z)-β-iodovinyl ketone has been achieved with the tandem formation of CC and CI bonds in a three-component reaction. This new catalysis utilizes MgI₂ as a Lewis acid as well as an iodine source for a Michael-type addition. α,β-Acetylenic ketone is initially converted to an active β-iodo allenolate intermediate and then can be attacked by a variety of aldehydes to afford Z-selective Baylis-Hillman adducts in excellent yields.     

Lewis base catalyzed, enantioselective aldol addition of methyl trichlorosilyl ketene acetal to ketones

The catalytic enantioselective addition of an acetate enolate equivalent to ketones is described. Methyl trichlorosilyl ketene acetal reacts with a wide range of ketones in the presence of pyridine N-oxide to afford the aldol addition products in excellent yields. Chiral 2,2'-pyridyl bis-N-oxides bearing various substituents at the 3,3'- and 6,6'-positions also provide excellent yields of the aldol products with variable enantioselectivities ranging from 94/6 er for aromatic ketones to nearly racemic for aliphatic ketones. An X-ray crystal structure of the complex between a catalyst and silicon tetrachloride (((P)-(R,R)-19.SiCl(4))) has been obtained. Extensive computational analysis provides a stereochemical rationale for the observed trends in enantioselectivities.     

New chiral bis(diphenylphospholane) ligands: design, synthesis, and application to catalytic enantioselective aldol reaction to ketones

New chiral bidentate diphenylphospholanes were designed targeting a catalytic enantioselective aldol reaction to ketones. Ligands 5l and 5m having cis-2-butenyl and cyclopropyl groups at the linker part, respectively, were identified as effective chiral ligands for a CuF-catalyzed enantioselective aldol reaction to ketones. Catalysts prepared from CuF·3PPh₃·2EtOH and these ligands produced ketone aldol products with up to 66% ee, which is promising particularly for this extremely difficult and important catalytic enantioselective carbon-carbon bond forming reaction. The enantioselectivity was strongly dependent on the linker structure. Construction of a deep chiral pocket around the copper metal with stable bidentate chelation is the key to meaningful enantioinduction.     

An efficient synthetic method for macrocyclic ketones by intramolecular alkylation of protected cyanohydrins,and its application to the syntheses of muscone and exaltone

A simple synthetic method for macrocyclic ketones based on intramolecular alkylation of carbanion, generated from protected cyanohydrin is reported. Subsequent mild treatment with acid and base of the cyclized products leads to macrocyclic ketones in high yields. The reaction is rapid and irreversible, and hence required short reaction time. The method was successfully applied to the syntheses of cyclohexadecanone and trans-2-cyclopentadecenone as a precursor of (±)-muscone and exaltone.     

An NMR method for assigning relative stereochemistry to beta-hydroxy ketones deriving from aldol reactions of methyl ketones

We describe a simple 1H NMR analysis that permits the stereochemistry of beta-hydroxy ketones to be assigned by visual inspection of the ABX patterns for the alpha-methylene unit of the beta-hydroxy ketone in the 1H NMR spectra. This method has been verified by application to a wide range of beta-hydroxy ketones deriving from aldol reactions of chiral aldehydes with a variety of chiral and achiral methyl ketone enolates (see Tables 1 and 2). The stereochemistry of 54 of these compounds have been assigned by rigorous chemical methods.     

A regioselective enolate formation of trimethylsilylmethyl ketones application to the (E)-selective synthesis of α,β-unsaturated ketones

Two possible enolate anions of trimethylsilylmethyl ketones have been prepared regioselectively by the appropriate choice of base. The one directed to the silylmethyl site behaves as a highly reactive and (E)-selective condensation reagent to aldehydes.     

Sequential aldol condensation-transition metal-catalyzed addition reactions of aldehydes, methyl ketones, and arylboronic acids

Sequential aldol condensation of aldehydes with methyl ketones followed by transition metal-catalyzed addition reactions of arylboronic acids to form β-substituted ketones is described. By using the 1,1'-spirobiindane-7,7'-diol (SPINOL)-based phosphite, an asymmetric version of this type of sequential reaction, with up to 92% ee, was also realized. Our study provided an efficient method to access β-substituted ketones and might lead to the development of other sequential/tandem reactions with transition metal-catalyzed addition reactions as the key step.     

Efficient synthesis of methyl 3,5-di-O-benzyl-alpha-D-ribofuranoside and application to the synthesis of 2'-C-beta-alkoxymethyluridines

Methyl 3,5-di-O-arylmethyl-alpha-D-ribofuranosides have been used extensively as synthons to construct 2'-C-branched ribonucleosides. Herein, we describe efficient access to methyl 3,5-di-O-arylmethyl-alpha-D-ribofuranosides (aryl: 2-ClC(6)H(4), 3-ClC(6)H(4), 4-ClC(6)H(4), 4-BrC(6)H(4), 2,4-Cl(2)C(6)H(3), Ph) in 72-82% yields from methyl D-ribofuranoside. We also demonstrate efficient access to the versatile precursor methyl 3,5-di-O-benzyl-alpha-D-ribofuranoside (3f) and the synthesis of 2'-C-beta-methoxymethyl- and 2'-C-beta-ethoxymethyluridine in six steps from 3f with overall yields of 18% and 32%, respectively.     

Direct synthesis of Cbz-protected β-amino ketones by iodine-catalyzed three-component condensation of aldehydes, ketones and benzyl carbamate

Iodine has been found to be very effective catalyst for a Mannich reaction between an aryl aldehyde, an aryl ketone and benzyl carbamate, even though this is a less reactive amine, to produce Cbz-protected β-aryl β-amino carbonyl compounds in high yields.