Synthesis and hetero-Diels-Alder reactions of (E)-α-perfluoroalkanesulfonyl-α,β-unsaturated ketones

Catalyzed by ammonium acetate, the Knoevenagel reactions of β-keto perfluoroalkanesulfones 1 with aromatic aldehydes 2 afforded α-perfluoroalkanesulfonyl-α,β-unsaturated ketones 4 in moderate to good yields. The possible mechanism for the reactions was proposed. These fluorine-containing α,β-unsaturated ketones, which are electron-poor 1-oxa-1,3-butadienes, could be used in inverse electron demand hetero Diels-Alder (HDA) reaction with electron-rich olefins to give tetrasubstituted dihydropyrans 6 in quantitative yields.     

SmI2-induced cyclization of optically active (E)- and (Z)-β-alkoxyvinyl sulfoxides with aldehydes

SmI₂-induced reaction of (E)-β-alkoxyvinyl (R)- and (S)-sulfoxides with aldehydes effected a highly stereoselective intramolecular cyclization to give 2,6-anti-2,3-cis- and 2,6-syn-2,3-trans-tetrahydropyran-3-ols, respectively. The reaction of (Z)-(R)-isomer gave 2,6-syn-2,3-cis-tetrahydropyran-3-ol and a ring-opened product, and that of (Z)-(S)-isomer yielded many products.     

A practical and efficient synthesis of (E)-β-aryl-α,β-unsaturated amides

In this paper, we report a one-step convergent synthesis of (E)-β-monosubstituted α,β-unsaturated amides 3 from α-sulfonyl acetamide 1 and benzyl bromide derivatives 2.     

Synthesis of (E)- and (Z)-α,β-difluorourocanic acid

Horner-Emmons fluoroolefination of an aryl aldehyde followed by introduction of a second fluorine via “FBr” addition provides an original approach to the preparation of 1-alkyl-2-aryl-1,2-difluoroethenes. The utility of this procedure is demonstrated by the preparation of (E and Z)-α,β-difluorourocanic acid.     

A general route to α-alkyl (E)-α,β-unsaturated aldehydes

Bis(trimethylsilyl)-tert-butylaldimines 3 react with aldehydes in the presence of zinc bromide at room temperature to give, after hydrolysis, the desired α-alkyl α,β-ethylenic aldehydes in good yield and with very high E stereoselectivity. The reaction was believed to proceed via the α-silyl β-siloxyimines 4.     

Self-supported BINOL-Zn catalysts for heterogeneous enantioselective epoxidation of (E)-α,β-unsaturated ketones

A class of chiral self-supported catalysts prepared from bis-BINOL ligands and diethyl zinc were successfully applied in the hetereogeneous enantioselective epoxidation of a range of (E)-α,β-unsaturated ketones, affording the corresponding epoxy ketones in high enantioselectivity. The self-supported catalysts were easily recovered from the reaction mixture and were reusable for several consecutive runs.     

An efficient synthesis of (E)-α,β-unsaturated ketones and esters with total stereoselectivity by using chromium dichloride

(E)-α,β-Unsaturated ketones 1 or esters 2 can be obtained with complete stereoselectivity by reaction of different 2-chloro-3-hydroxy ketones 3 or esters 4 and CrCl₂. A comparative study of the results of synthesis of ketones 1 with CrCl₂ or samarium is performed. A mechanism to explain both β-elimination reactions has been proposed.     

Solvent-free heterogeneous organocatalysis: stereoselective isomerization of α,β-ynones to (E,E)-α,β-γ,δ-dienones catalyzed by polymer-supported tertiaryphosphines

Stereoselective isomerization of α,β-ynones was catalyzed by polymer-supported tertiaryphosphines under solvent-free conditions. (E,E)-α,β-γ,δ-Dienones were obtained with up to 93% isolated yields when JJ-TPP was employed.     

Synthesis and hydrogenation of (E)-γ-aryl-γ-morpholino-α-trifluoromethylated allyl alcohols through the reaction of trifluoroacetaldehyde ethyl hemiacetal with enamines

Treatment of trifluoroacetaldehyde ethyl hemiacetal with enamines, derived from acetophenone derivatives, at room temperature gave (E)-1,1,1-trifluoro-4-morpholino-4-aryl-but-3-en-2-ols, which are intermediates for preparation of the β-trifluoromethylated aldol products, 4,4,4-trifluoro-3-hydroxy-1-aryl-butan-1-ones. The structure of the intermediate (E)-1,1,1-trifluoro-4-morpholino-4-(4-nitrophenyl)-but-3-en-2-ols could be assigned by ¹H, ¹³C NMR, IR, and X-ray crystallography. Furthermore, hydrogenation and reductive deamination of the intermediate (E)-1,1,1-trifluoro-4-morpholino-4-aryl-but-3-en-2-ols with hydrogen in the presence of a catalytic amount (10 mol %) of palladium on carbon in trifluoroethanol proceeded smoothly at room temperature to give 1,1,1-trifluoro-4-aryl-2-butanols in good to excellent yields.     

A facile stereoselective synthesis of (Z)-α-arylsulfonyl-α,β-unsaturated ketones

Palladium-catalyzed hydrostannylation of acetylenic sulfones 1 in benzene at room temperature gives highly regio- and stereoselectively (E)-α-stannylvinyl sulfones 2 in high yields. (E)-α-Stannylvinyl sulfones 2 are new difunctional group reagents which undergo Stille coupling reactions with acyl chlorides 3 to afford stereoselectively (Z)-α-arylsulfonyl-α,β-unsaturated ketones 4 in good yields. A one-pot stereoselective synthesis of (Z)-α-arylsulfonyl-α,β-unsaturated ketones 4 has also been achieved by tandem hydrostannylation-Stille coupling reaction of acetylenic sulfones 1 under mild conditions.     

Synthesis of (Z)-α-chloro-α,β-unsaturated esters with complete stereoselectivity promoted by samarium diiodide

Stereoselective β-elimination in α,α-dichloro-β-hydroxyesters 2 was achieved by using samarium diiodide, yielding (Z)-α-chloro-α,β-unsaturated esters 1. The starting compounds 2 were easily prepared by reaction of the lithium enolate of ethyl dichloroacetate with different aldehydes at −78 °C. A mechanism to explain this process is proposed.     

Highly stereoselective synthesis of trans-4-trifluoromethylsulfonyl-2,3-dihydrofurans from arsonium ylides and (E)-α-trifluoromethylsulfonyl-α,β-unsaturated ketones

The reactions of arsonium bromides with (E)-α-trifluoromethylsulfonyl-α,β-unsaturated ketones in the presence of Cs₂CO₃ or K₂CO₃ proceeded smoothly under refluxing condition in dichloromethane (DCM) to give the corresponding trifluoromethylated trans-2,3-dihydrofurans in good to excellent yields with high stereoselectivity.     

Asymmetric organocatalytic Michael/α-alkylation reaction of α,β-unsaturated aldehyde with chloroacetophenone

Asymmetric organocatalytic Michael/α-alkylation reactions of α,β-unsaturated aldehydes with chloroacetophenones have been developed. The biologically useful cyclopropane motifs were synthesized with high yields and up to >99% ee, >30:1 dr through Jørgensen-Hayashi catalyst under mild conditions.     

Aerobic copper-catalyzed synthesis of (E)-alkenyl sulfones and (E)-β-halo-alkenyl sulfones via addition of sodium sulfinates to alkynes

Copper-catalyzed sulfonylation of alkynes using sodium sulfinates in air produced regio- and stereoselectively (E)-alkenyl sulfones. When a CuCl catalyst was employed, the hydrosulfonylation proceeded syn-selectively, and (E)-alkenyl sulfones were synthesized in excellent yields. In contrast, the reaction using CuI catalyst produced (E)-β-haloalkenyl sulfones anti-selectively in the presence of potassium halides. Furthermore, the (E)-β-bromoalkenyl sulfones are possible to convert into various alkenyl sulfones by Suzuki–Miyaura coupling.     

Phosphine-mediated diverse reactivity of γ-substituted allenoates with aldehydes: syntheses of highly functionalized chromans and (E,E)-1,3-dienes

As an extension of our previous studies, the phosphine-mediated diverse reactivity of γ-substituted allenoates with aldehydes has been further investigated. Under the catalysis of tris(p-chlorophenyl)phosphine (20 mol %), ethyl 2,3-pentadienoate, namely ethyl γ-methyl allenoate, readily undergoes a formal [4+2] annulation with dual-functional salicylaldehydes, giving highly functionalized chromans in 47-97% yields. This transformation represents a novel reactivity pattern of electron-deficient allenes with aldehydes. Conversely, when the γ substituent in the allenoate changes from methyl to benzyl or the employed phosphine from weakly nucleophilic triarylphosphine to strongly trialkylphosphine, the phosphine-mediated reactivity of γ-substituted allenoates with aldehydes will be steered to a stoichiometric olefination reaction, leading to the highly stereoselective formation of (E,E)-1,3-dienes. Thus, under the mediation of equivalent PPh₃, ethyl γ-benzyl allenoate readily condenses with salicylaldehydes, affording (E,E)-1,3-dienes in 34-84% yields; with strongly nucleophilic 1,3,5-triaza-7-phosphaadamantane (PTA) used instead of PPh₃, ethyl γ-methyl allenoate also gives the corresponding olefination products in 32-73% yields with reactive aromatic aldehydes. On the basis of our previous studies and current work, these chemical transformations of γ-substituted allenoates with aldehydes, as well as their diverse reactivity, have been mechanistically rationalized.     

Catalytic enantioselective synthesis of optically active α-hydroxyl-β,γ-unsaturated acid esters as novel side chains of cerebrosides

Six optically active α-hydroxyl-β,γ-unsaturated acid esters 1a to 1f were synthesised, and they are significant moieties of the cerebrosides. The chiral intermediate alkynol 4 prepared by catalytic asymmetric addition had 99% ee, and which was converted into the target compounds 1a to 1f with high enantiomeric purity.     

Lewis acid-promoted reaction of β,γ-unsaturated α,α-dimethoxy esters with silyl nucleophiles

The Lewis acid-promoted reaction of β,γ-unsaturated α,α-dimethoxy esters, which are easily prepared by the acetalization of β,γ-unsaturated α-keto esters, with silyl nucleophiles is presented. By employing trimethylsilyl enolate and allyltrimethylsilane as nucleophiles, the BF₃-promoted reactions of a series of β,γ-unsaturated α,α-dimethoxy esters bearing aromatic and aliphatic substituents proceeded at the γ-position in an SN2′ manner to furnish γ-substituted α,β-unsaturated α-methoxy esters in good yields with high regioselectivity. In contrast, the reaction using trimethylsilyl cyanide predominantly occurred at the α-position, and the reaction of silyl hydride resulted in a mixture of α- and γ-regioisomers in favor of the γ-substitution products.     

TiCl4-mediated olefination of aldehydes with acetic acid and alkyl acetates: a stereoselective approach to (E)-α,β-unsaturated carboxylic acids and esters

A new method has been developed for the preparation of α,β-unsaturated carboxylic acids and corresponding esters with (E)-stereoselectivity via the TiCl₄-mediated olefination of aldehydes. The method, which uses readily available acetic acid or its alkyl esters as active methylene partners, is more flexible and complementary to conventional routes in the preparation of (E)-cinnamic acid derivatives.     

α-Bromo-β,γ-unsaturated ketenes for the synthesis of α-benzylamino-β,γ-unsaturated acids

The synthesis of α-benzylamino-β,γ-unsaturated acids has been developed starting from α-bromo-α,β-unsaturated chlorides. Via treatment of the acyl chlorides with (R)-pantolactone in the presence of TEA, the in situ formation of the deconjugated ketenes and their direct transformation into chiral esters was performed. The substitution of bromine with benzylamine, followed by acid hydrolysis, allowed to us obtain enantiomerically enriched α-benzylamino-β,γ-unsaturated acids.