Organocatalytic direct asymmetric vinylogous Michael reaction of an α,β-unsaturated γ-butyrolactam with enones

An organocatalytic asymmetric direct vinylogous Michael addition of α,β-unsaturated γ-butyrolactam to enones has been achieved with a simple bifunctional thiourea-tertiary amine catalyst, affording the γ-substituted butyrolactam products with high diastereo- and enantioselectivity (up to >40:1 dr and 94-99% ee).     

The efficient consecutive β-carboxylation and α-alkylation of cyclic α,β-enones; a new route to sarkomycin

Sequential one-pot introduction of a carboxy group equivalent and an alkyl group at the respective β- and α-positions of cyclic enones has been achieved through a 1,4-addition reaction of [methoxy(phenylthio)(trimethylsilyl)methyl] lithium followed by direct trapping of the resulting enolate with alkyl halides. The present method proved to be applicable to a simple synthesis of sarkomycin.     

Application of chiral ionic liquids in the copper catalyzed enantioselective 1,4-addition of diethylzinc to enones

Copper catalyzed enantioselective addition of diethylzinc to various enones has been achieved in the presence of a new class of chiral ionic liquid (ChirILs) derived from α-pinene. This first study on the application of ChirILs for the title reaction shows that the chiral reaction medium has a significant influence on chiral induction.     

Enantioselective N‐Heterocyclic Carbene Catalysis by the Umpolung of α,β‐Unsaturated Ketones

N‐Heterocyclic carbene‐catalyzed formation of β‐anionic intermediates from enones has been employed in the enantioselective synthesis of 2‐aryl propionates. The reaction was achievable using a homochiral 4‐MeOC₆H₄ morpholinone catalyst allowing the first example of enantioselective catalysis by umpolung of α,β‐unsaturated ketones. The reaction is high yielding, and shows robustness with reasonable generality. A mechanism is proposed in which the enantiodetermining protonation is achieved using either hexafluoroisopropanol or the formed naphthol product.     

Regioselective reductions of β,β-disubstituted enones catalyzed by nonracemically ligated copper hydride

CuH-catalyzed 1,2-additions to β,β-disubstituted α,β-unsaturated ketones have been further explored. Asymmetric reductions of enones lacking an α-substituent can be achieved with CuH complexed by DTBM-SEGPHOS in Et₂O at ?25 °C leading to the generation of highly valuable nonracemic allylic alcohols. The corresponding 1,4-reductions can also be achieved using the same reaction conditions by switching the ligand to a JOSIPHOS analog affording nonracemic β,β-disubstituted ketones. DFT calculations of the enone conformations and transition-state energies for model 1,2- and 1,4-additions were carried out to clarify the factors affecting the product ratios.     

Synthesis of novel β-functionalized α-oximinoketones via hetero-Michael addition of alcohols and mercaptans to enones

A new methodology has been developed for the preparation of β-alkoxy and β-sulfenyl ketones by hetero-Michael addition of the corresponding alcohols and thiols to enones under acidic and basic conditions. The direct conversion of enones into β-alkoxy and β-sulfenyl α-oximinoketones was also described.     

A new and efficient chemoenzymatic route to both enantiomers of α′-acetoxy and α′-hydroxy-α-methoxy cyclic enones

A chemoenzymatic synthesis of both enantiomers of the pharmacologically interesting α′-acetoxy and α′-hydroxy-α-methoxy cyclic enones starting from α-hydroxy cyclic enones is described. Protection of 1,2-diketones, manganese(III) acetate-mediated acetoxylation followed by enzyme-mediated hydrolysis of α′-acetoxy enones gives acetoxy enones 3a–d and hydroxy enones 4a–d with high enantiomeric excesses (up to 99%) and good yields. The transesterification of rac-4b in the presence of DMAP afforded (+)-4b and (−)-3b in high enantiomeric excesses (91–94%) and good chemical yields.     

A new procedure for α-alkoxyalkylation of α,β -unsaturated ketones

A one-pot procedure for α-alkoxyalkylation of α,β-unsaturated ketones has been devised, which by combination with the organocopper conjugate addition reaction provides a new tool for vicinal carba-condensation of enones.     

Chiral Brønsted Acid Directed Iron‐Catalyzed Enantioselective Friedel–Crafts Alkylation of Indoles with β‐Aryl α′‐Hydroxy Enones

A cooperative catalytic system established by the combination of an iron salt and a chiral Brønsted acid has proven to be effective in the asymmetric Friedel–Crafts alkylation of indoles with β‐aryl α′‐hydroxy enones. Good to excellent yields and enatioselectivities were observed for a variety of α′‐hydroxy enones and indoles, particularly for the β‐aryl α′‐hydroxy enones bearing an electron‐withdrawing group at the para position of the phenyl ring (up to 90 % yield and 91 % ee). The proton of the chiral Brønsted acid, the Lewis acid activation site, as well as the inherent basic site for the hydrogen‐bonding interaction of the Brønsted acid are responsible for the high catalytic activities and enantioselectivities of the title reaction. A possible reaction mechanism was proposed. The key catalytic species in the catalytic system, the phosphate salt of Fe^III, which was thought to be responsible for the high activity and good enantioselectivity, was then confirmed by ESIMS studies.     

Étude comparative,par spectroscopie infrarouge,des vibrations v(ch) de quelques alcools et thiols ne comportant qu'un seul vibrateur ch

Infrared spectra of some deuterated alcohols and thiols with only one α-CH or β-CH have been obtained in order to compare α and β heteroatom effects on v(CH). The spectra of RR'CHOH alcohols show two bands (Δv? 50 cm^?1) due to the α-CH bond trans to an oxygen lone-pair and the α-CH bond trans to OH.The α sulphur effect is found very weak or non-existent in thiols. The study of CD₂H-CD ₂OH and CD₂HCD₂SH spectra shows the same β-gauche effect of both the heteroatoms while only the sulphur atom seems to have a β-trans effect.     

Mechanistic study of asymmetric Michael addition of malonates to enones catalyzed by a primary amino acid lithium salt

A mechanistic study was carried out for the asymmetric Michael addition reaction of malonates to enones catalyzed by a primary amino acid lithium salt to elucidate the origin of the asymmetric induction. A primary β-amino acid salt catalyst, O-TBDPS β-homoserine lithium salt, exhibited much higher enantioselectivity than that achieved with the corresponding catalysts derived from α- and γ-amino acids for this reaction. Detailed studies of the transition states with DFT calculations revealed that the lithium cation and carboxylate group of the β-amino acid salt catalyst have important roles in achieving high enantioselectivity in the Michael addition reaction of malonates to enones.     

Surveying approaches to the formation of carbon-carbon bonds between a pyran and an adjacent ring

We have examined several methods for the stereoselective formation of carbon-carbon bonds between contiguous rings where a stereogenic center is already present. The approaches investigated were a [1,3] oxygen to carbon rearrangement of cyclic vinyl acetals, an intermolecular enolsilane addition into an in situ generated oxocarbenium ion, an intramolecular conjugate addition of tethered alkoxy enones, and epimerization of several α-pyranyl cycloalkanones. These routes have been found to be complementary in several cases and have enabled formation of both the trans:anti and cis:anti stereoisomers in good to excellent yields and varying diastereoselectivities. We have proven C2-C2′ relative stereochemistry of 1-2 via a chemical correlation.     

Cyanation of α,β-unsaturated enones by malononitrile in open air under metal-catalyst-free conditions

Cyanation of α,β-unsaturated enones by employing malononitrile as the organic cyanation source has been disclosed, which proceeds efficiently at room temperature in open air under metal-catalyst-free conditions.     

One-pot consecutive reactions based on the synthesis of conjugated enones by the re-catalysed meyer-schuster rearrangement

Re catalysis in one-pot reactions: An atom-economical, one-pot strategy that involves alkyne deprotonation and a subsequent rhenium(V)-catalysed Meyer-Schuster rearrangement of the alkynol to provide α,?-unsaturated enones in high yield has been developed. Subsequent in situ hydride reduction or Diels-Alder reaction of the enones provided products in good-to-high overall yields.     

Highly efficient epoxidation of electron-deficient olefins with tetrabutylammonium peroxydisulfate

The epoxidation of α,β-unsaturated carbonyl compounds such as enones and enals was efficiently achieved with tetrabutylammonium peroxydisulfate in the presence of equimolar amounts of hydrogen peroxide and NaOH in acetonitrile or methanol at 25 °C in excellent yields. Base-sensitive substrate such as cinnamaldehyde could be successfully epoxidized in short reaction time under mild reaction conditions.     

Efficient Brønsted acid-catalyzed aza-Michael reaction of amides and ureas with α,β-unsaturated enones under high-pressure conditions

A new strategy for the aza-Michael reaction of amides and ureas with α,β-unsaturated enones, which uses p-TsOH·H₂O as an efficient and inexpensive catalyst under high-pressure conditions, has been developed.     

Acyclic stereocontrol by heteroconjugate addition—4 : Anti-diastereoselection by a β-chelation effect

High selectivity in heteroconjugate addition for C—C bond formation with complete syndiastereoselection has been attributed to the chelation effect between the α-oxygen atom of the substrate and the nucleophile anions through metal cations. Herein is described a new method exhibiting antidiastereoselection based on a different chelation effect caused by the ligands on the β-carbon atom to the heteroolefin. Most of the examples are taken as the heteroolefin connected at the C-5 position to D-hexopyranosides with a C-4 hydroxyl group. Thus, the methodology was expanded to an optically active system starting from glucose as a chiral source for asymmetric synthesis. The results are very clear in the case of a Grignard reagent as the nucleophile instead of methyllithium, and so one of the compounds was used for the synthesis of the A-segment of okadaic acid.     

Enantioselective conjugate addition of diethylzinc to acyclic enones using a copper phosphino-phenol complex as catalyst

Newly designed phosphino-phenol 1c was found to be an efficient chiral auxiliary for copper-mediated asymmetric conjugate addition of diethylzinc to acyclic enones. High enantioselectivity up to >99% ee was achieved in the reaction of acyclic α,β-enones.     

Enantioselective addition of methyllithium to aromatic imines catalyzed by C2 symmetric tertiary diamines

Enantioselective addition of methyllithium to aromatic imines catalyzed by C₂ symmetric tertiary diamines is described. Eleven diamines have been tested, for which dramatic effect of the nitrogen substitution has been observed. Diamines bearing hindered group close to the nitrogen led to racemic product while homologous hindered diamines led to the best results. Enantiomeric excess up to 74% could be achieved. An explanation of the absolute configuration of the product obtained is given considering the mechanism of the reaction.     

The addition of perfluoroalkanesulfinyl chlorides to alkoxyallenes

The addition reaction of perfluoroalkanesulfinyl chlorides to alkoxyallenes was achieved under mild conditions. Two kinds of perfluoroalkyl alkenyl sulfoxides, β-alkoxyvinyl perfluoroalkyl sulfoxides and α-perfluoroalkanesulfinyl enones or enals, were obtained selectively depending on the structure of alkoxyallenes.