Synthese stereoselective d'esters α,β- ethyleniques α-methyles Z ou E par la reaction de wittig-horner a partir de phosphonates ou d'oxydes de phosphine

The reaction of α-branched aldehydes with diethyl 1-carbomethoxyethyl phosphonate 1b in THF/nBuLi at low temperature leads stereoselectively to Z α-methyl α,β-unsaturated esters. From a linear aldehyde, the reaction is less stereoselective, while from α,β-unsaturated ones, the E isomers are predominantly formed in good yields. From diphenyl 1-carbomethoxyethyl phosphine oxide 2b, E α-methyl α,β-unsaturated esters are stereoselectively formed either in DMF/tBuOK or in phase transfer conditions, whatever the starting aldehyde is, also in good yields. This reagent can thus advantageously replace the corresponding P-ylid. In all cases, the reaction conditions are determined so that by-products formation is minimized.     

A highly stereoselective synthesis of α,β-unsaturated oxazolines

Lithiated 2,4,4-trimethyl-2-oxazoline 2a and 2-chloromethyl-4,4-dimethyl-2-oxazoline 2b react smoothly with a number of nitrones 3 to produce α,β-unsaturated oxazolines 6 and 7 highly stereoselectively.     

A practical and enantiospecific conversion of d-galactose to a substituted α,β-unsaturated δ-lactone synthon

A multi-gram synthesis of a substituted α,β-unsaturated δ-lactone synthon, 1, was developed from commercially available d-galactose. The use of a Horner–Wadsworth–Emmons reaction was able to furnish, with Z selectivity, the enone ester that spontaneously lactonised to provide enantiomerically pure 1.     

Regioselective SN′ allylic substitution versus 1,4-addition: Synthesis of α-substituted β,γ-unsaturated esters

The reaction of the higher order organocuprate reagents R₂Cu(CN)Li₂-BF₃ with γ-bromo α,β-unsaturated esters gives with very high selectivity α-substituted β,γ-unsaturated esters arising from a SN′ allylic substitution. This reaction allows an easy access to α-silyl β,γ-unsaturated esters.     

Knoevenagel condensation of α,βunsaturated aromatic aldehydes with barbituric acid under non-catalytic and solvent-free conditions

An efficient route for the synthesis of 5-(arylpropenylidine)-2,4,6-pyrimidinetrione 3 from an appropriateα,β-unsaturated aromatic aldehydes 1 and barbituric acid 2 under both non-catalytic and solvent-free microwave irradiation conditions was described.In this way,a range of biologically important compounds 3 was obtained in good to excellent yields (86-98%) in a very short reaction time (30-80s).     

Additive Pummerer reactions of vinylic sulfoxides. Synthesis of γ-hydroxy-α,β-unsaturated esters, α-hydroxyketones, and 2-phenylsulfenyl aldehydes and primary alcohols

Treatment of β-monosubstituted vinylic sulfoxides 1 with trifluoroacetic anhydride in dichloromethane gave excellent yields of 1,2-bis(trifluoroacetoxy)thioethers 6. Mildly basic methanolysis of 2-alkyl-substituted 6 gave α-hydroxyaldehydes 11 as monomer-dimer mixtures; similar treatment of the 2-aryl analogues afforded aryl (hydroxymethyl) ketones 12. Compounds 11 underwent Wittig reactions with methoxycarbonylmethylenetriphenylphosphorane to give high yields of γ-hydroxy-α,β-unsaturated esters 13, predominantly as the E-isomers. β-Monosubstituted vinylic sulfoxides 1 possessing a β-aryl group, and β-disubstituted vinylic sulfoxides 3 reacted with trifluoromethanesulfonic anhydride-sodium acetate in acetic anhydride to give 2-(phenylsulfenyl)acylals 14. These gave 2-phenylsulfenyl aldehydes 15 upon basic methanolysis, and the corresponding primary alcohols 16 on reduction with sodium borohydride. Reaction of both geometric isomers of enantiomerically pure vinylic sulfoxide 1o with TFAA gave racemic 6o as a mixture of diastereomers. Reaction of optically pure (E)- and (Z)-1p with trifluoromethanesulfonic anhydride-sodium acetate in acetic anhydride gave acylal 19 in 10.5 and 23% e.e., respectively.     

The first example of α-organoseleno arsonium ylides and its Wittig-type reaction

α-Organoseleno arsonium ylide 3 was synthesized for the first time by a phenylselenenylation-transylidation reaction. It has sufficient activity to carry out the Wittig-type reaction, affording a novel method for the stereoselective synthesis of (Z)-α-phenyl-seleno-α, β-unsaturated esters 6.     

Addition of trimethylsilylmethylmagnesium chloride to α, β-unsaturated carbonyls

Reactions of α,β-unsaturated carbonyl compounds with Me₃SiCH₂MgCl, prepared from chloromethyltrimethylsilane [1], were examined. Unlike its lithium counterpart (Me₃SiCH₂Li), which adds to α,β-unsaturatedketones in the 1,2-sense, the Grignard reagent afforts γ silanes via a 1,4-addition sequence. This tendency is accentuated by the addition of Cu₂Br₂. Addition of the Grignard reagent to α,β-unsaturated aldehydes gives the simple 1,2-addition products.     

Synthesis of α,β-unsaturated ketone from α-iodo ketone using photoirradiation

Irradiation of α-iodo ketone in hexane under a nitrogen atmosphere with a high-pressure mercury lamp (λ>300nm) at room temperature afforded the corresponding α,β-unsaturated ketones in good yield. This reaction affords a new, clean and convenient synthetic method for the α,β-unsaturated ketone.     

The clemmensen reduction of α,β-unsaturated ketones

The deoxygenation of the α,β-unsaturated ketones (1) and (5) under the Clemmensen condition yielded the olefins (2) and (6) along with their respective dimers (3+4) and (8+9). The α , β-unsaturated ketone (13) under similar treatment yielded the olefin (14) in satisfactory yield but the dimer could not be characterized. The deoxygenation of the α,β-unsaturated ketones (10) and (16) under similar con- ditions afforded the olefins (12) and (15) respectively in satisfactory yield along with the rearranged olefins (11) and (17) respectively. Epox-idation of the olefin (17) followed by heating with p-toluenesulfonic acid yielded the ketone (18).     

Biosynthesis of aristeromycln: Evidence for the intermediacy of a 4β-hydroxymethyl-1α, 2α, 3α-trihydroxycyclopentanetriol.

Evidence for the intermediacy of a 4β-hydroxymethyl-1α, 2α, 3α-trihydroxycyclopentanetdol (5 or6) in the biosynthesis of the nucleoside antibiotic aristeromycin (1) has been obtained by administration of doubly-labeled forms of D-glucose to the fermentation broth ofStreptomyces citricolor followed by trapping of the tetrol5 using isotope dilution methods.     

Chlorination of α-sulfonyl carbanions with hexachloroethane: A novel preparation of α-halosulfones

The cyclic sulfones1,2, and3 are lithiated in benzene with n-butyllithium. Lithiation is demonstrated to lead to α-mono, α,α′-di and/or α,α-di and α,α,α′ trimetallation. The lithiated sulfones are chlorinated with hexachloroethane (HCE). Some mechanistic aspects of the reaction of the lithiosulfones with vicinal dihalides are discussed.     

An efficient method for the stereoselective synthesis of cis-3-substituted prolines: conformationally constrained α-amino acids

An efficient synthesis of enantiomerically pure cis-3-substituted prolines is reported. Key steps involve the stereoselective organocuprate addition to the (E)-α,β-unsaturated ester 1, obtained from the Garner's aldehyde, and expedient oxidation–cyclization sequences.     

Diastereoselective SmI2-mediated cyclisation of δ-oxo-α,β-unsaturated esters to cyclopropanols

In the presence of samarium diiodide and a proton source, δ-oxo-γ,γ-disubstituted-α,β-unsaturated esters readily cyclise with complete diastereocontrol to give anti-cyclopropanol products.     

Catalytic asymmetric epoxidation of α,β-unsaturated carboxylic acid imidazolides and amides by lanthanide–BINOL complexes

Highly enantioselective catalytic asymmetric epoxidation of α,β-unsaturated carboxylic acid imidazolides and simple amides was developed. In the presence of 5–10 mol% of lanthanide–BINOL complexes, the reaction proceeded smoothly with high substrate generality. In particular, in the cases of α,β-unsaturated amides, there was nearly perfect enantioselectivity (>99% ee). The corresponding epoxides were successfully transformed into many types of useful chiral compounds such as α,β-epoxy esters, α,β-epoxy amides, α,β-epoxy aldehydes, α,β-epoxy β-keto ester, and α- and β-hydroxy carbonyl compounds. B3LYP density functional studies were performed to predict substrate reactivity.     

1,4-addition reactions to α,β unsaturated tertiary amides

Ketones, phenylacetonitrile, ethylmalonate, cyanoethyl acetate, nitromethane and nitroethane were found to add directely to α,β-unsaturated tertiary amides in the presence of CsF/Si(OMe)₄ to give 1,4-addition products in fair to good yields.     

Synthesis of α,β-unsaturated aryl esters via Heck reaction of unsymmetrical aryl tellurides

A variety of α,β-unsaturated aryl esters were prepared by the direct reaction of unsymmetrical aryltellurides and ethyl acrylate, catalyzed by PdCl₂ via a Heck cross-coupling reaction.     

Cycloaddition reactions of sulfonylisothiocyanates with β,β-disubstituted enamines

Sulfonylisothiocyanates 1 and β,β-dimethylenamines 2 react to yield the dipoles 3. In nonpolar solvents an equilibrium exists between 3 and the thietanes 4. The free activation enthalpy for the ring closure 3→4 was obtained from the temperature dependent NMR spectra in liquid sulfur dioxide. Protonation of 3 with perchloric acid leads to the salts 8 which, as indicated by ΔG^≠-values obtained from NMR spectra, are also capable of ring closure.     

Syntheses of methyl α-dl-mycaminoside, methyl α-dl-oleandroside, methyl β-dl-cymaroside, methyl α-dl-tyveloside and methyl α-dl-chromoside C

Five rare hexoses, which are components of antibiotics or cardiac glycosides, have been synthesized as methyl glycosides through a common intermediate methyl 2,3-dehydro-2,3,6-trideoxy-α-dl glucopyranoside (7). Epoxidation and subsequent treatment with dimethylamine of7 afforded methyl α-dl-mycaminoside (9). The addition reaction of MeOH to12 gave methyl α-dl-oleandroside (15) and methyl β-dl-cymaroside (17). The hydroxymercuration and subsequent reduction of12 afforded methyl α-dl-chromoside C (19) and methyl β-dl-tyveloside (25).     

The first enzymatic resolution of quaternary α′-acetoxy α,β-unsaturated cyclohexenones and cyclopentenones

The enantioselective resolution of various quaternary α′-acetoxy α,β-unsaturated cyclohexenones and cyclopentenones was performed with the commercially available enzyme CCL in pH = 8.0 phosphate buffer. Various parameters that would affect the enantioselectivities were tested and the best enzymatic resolution conditions were found to afford the enantiomerically enriched quaternary acetoxylated substrates with high ee varying between 36% and 99%.