Synthesis of axially dissymmetric 3,5-octadiene framework with C2 chirality via palladium(II)-catalyzed twofold [3,3]sigmatropic rearrangement

Palladium(Il)-catalyzed [3,3]sigmatropic rearrangement of (4R,5R)-4,5-(bisacetoxy)-1,8- (bisbenzyloxy)-2(E),6(E)-octadiene has proceeded convergently to give (2S,7S)-2,7-(bisacetoxy)-1,8(bisbenzyloxy)-3(E),5(E)-octadiene, translating the original chirality completely to the migration termini, which constitutes a novel synthesis of optically pure 3,5-octadiene with C₂ chirality.     

Asymmetric [2,3] Wittig rearrangement of crotyl furfuryl ethers

Asymmetric Wittig rearrangement of crotyl furfuryl ethers was investigated in diastereo- and enantioselective manners. Both (2S,3Z)- and (2S,3E)-3-penten-2-yl furfuryl ethers 3 and 9 rearranged with complete chirality transfer to give the syn- and anti-isomers 4 and 10, respectively. Enantioselective Wittig rearrangement of both (Z)-and (E)-crotyl furfuryl ethers 15 and 17 using butyllithium and (−)-sparteine was examined to afford (1S,2R)-1-(2-furyl)-2-methyl-3-buten-ol 16 in up to 43% ee.     

Rearrangement with oxide ion transfer in reactions of 4-chloro-2-oxo-2,3-dihydrothiazole-5-carbaldehyde with ureas. cis-(Z)-trans-(E) isomerism of N-(2,4-dioxothiazolidin-5-ylidenemethyl)ureas

4-Chloro-2-oxo-2,3-dihydrothiazole-5-carbaldehyde reacted with monosubstituted ureas to give cis-(Z)-and trans-(E)-N-(2,4-dioxothiazolidin-5-ylidenemethyl)ureas via rearrangement involving oxide ion transfer, cis (Z) Isomers were formed in methanol or dimethylformamide, while both individual cis (Z) and trans (E) isomers and their mixtures were isolated in the reaction performed in acetic acid.     

Enantioselective synthesis of the carbocyclic moiety of (−)-carbovir

Enantioselective construction of the protected carbocycle moiety of the anti-HIV drug carbovir was achieved in 11 steps from (S)-(−)-ethyl lactate. The two key steps are a Claisen [3+3] sigmatropic rearrangement of (3S,4E)-3-(4-methoxy-phenoxymethyl)-hex-4-enoic acid dimethylamide and next, a ruthenium-catalysed ring closure metathesis leading to (1S,4S)-4-(4-methoxy-phenoxymethyl)-cyclopent-2-enol.     

Diastereoselective rhodium(II)-catalyzed sulfonium ylide formation-[2,3]-sigmatropic rearrangement reaction of chiral non-racemic allylic sulfides

The tandem sulfonium ylide formation-[2,3]-sigmatropic rearrangement reaction of chiral non-racemic secondary allylic sulfides, (E)-9 and (Z)-10, is found to proceed with high diastereocontrol. The C-5 stereocenter bearing the sulfide group is essential for high diastereoselectivity in the reaction. Transition state conformers are proposed to explain the high diastereoselectivity in the formation of the diastereomeric products, 18a and 18b. The method is applied to the synthesis of (R)-4-(4-chlorophenyl)-2-butyrolactone. Modest enantioselectivity (63% ee) was achieved and this is attributed to partial racemization during the formation of the secondary allylic sulfide 22.     

Facial selectivity of the Ireland-Claisen rearrangement of allylic esters of 2-methyl and 2-methoxycyclopentanecarboxylic acids

Ketene silylacetals derived from prenyl and (Z)- and (E)-crotyl 2-methylcyclopentanecarboxylates (9) were subjected to the Ireland-Claisen rearrangement. All three substrates rearranged with complete facial selectivity, but the (Z)- and (E)-crotyl systems gave a mixture comprised of the same diastereomers of 1-(1-methyl-2-propenyl)-2-methylcyclopentanecarboxylic acid (14) in ratios of 2:1 and 1:2, respectively. In contrast, the ketene silylacetals prepared from allyl and prenyl 2-methoxycyclopentanecarboxylates (22) underwent rearrangements with both facial stereochemistries.     

Reactions of 1,1,1-trihalo-3-nitrobut-2-enes with enamines derived from cycloalkanones. Rearrangement of trifluoromethylated 1,2-oxazine N-oxide into 1-pyrroline N-oxides and stereochemistry of the products

1,2-Oxazine N-oxides derived from (E)-1,1,1-trifluoro-3-nitrobut-2-ene and cyclohexanone enamines underwent spontaneous rearrangement with ring contraction to give 1-pyrroline N-oxides. Reactions of (E)-1,1,1-trifluoro(trichloro)-3-nitrobut-2-enes with N-cyclopent-enylmorpholine resulted in a series of novel CX₃-containing nitroalkyl enamines and g-nitro ketones; the stereochemistry of the synthesized compounds were studied by NMR spectroscopy and X-ray diffraction.     

Functionalized β-lactams based on (<Emphasis Type="Italic">E</Emphasis>)-1-(furan-2-yl)-<Emphasis Type="Italic">N</Emphasis>-[(4-methoxyphenyl)methyl]methanimine and its imine–imine rearrangement initiated by potassium hydride

Functionalized β-lactams were synthesized by reaction of (E)-1-(furan-2-yl)-N-[(4-methoxyphenyl)-methyl]methanimine with ketenes generated in situ from chloro- and dichloroacetic acids and 3-(methoxyimino) butanoic acid. (E)-1-(Furan-2-yl)-N-[(4-methoxyphenyl)methyl]methanimine underwent imine–imine rearrangement by the action of potassium hydride to give thermodynamically more stable (E)-N-[(furan-2-yl)-methyl]-1-(4-methoxyphenyl)methanimine.     

A highly stereoselective transformation of carboxylic esters to trisubstituted olefins via cationic cyclopropyl-allyl rearrangement of sulfonates of cis-1,2-disubstituted cyclopropanols

Methanesulfonates of readily available cis-1,2-disubstituted cyclopropanols on reaction with magnesium bromide in diethyl ether undergo cyclopropyl-allyl rearrangement to afford allyl bromides, with an (E)-trisubstituted double bond, as main products. The amount of the corresponding (Z)-isomers did not exceed 5% when the reaction was performed at 0 °C, and the major concomitant products were the regioisomeric secondary bromides. The latter are sufficiently less reactive towards sulfur, phosphorus and hydrogen nucleophiles than the dominant (E)-disubstituted allyl bromides and these reactions are suitable for the stereoselective preparation of trisubstituted olefins.     

Haval-Argade contrathermodynamic rearrangement of alkylidenesuccinimides to alkylmaleimides via the corresponding isoimides: a general approach to alkyl and dialkyl substituted maleimides

A simple and efficient access to alkyl and dialkyl substituted maleimides has been demonstrated via the new contrathermodynamic rearrangement of (E)-alkylidenesuccinimides to alkylmaleimides. The (E)-alkylidenesuccinimides obtained from the Wittig-condensation of N-arylmaleimide with aliphatic aldehydes on regioselective hydrolysis furnished the corresponding (E)-alkylidenesuccinanilic acids in 95-98% yields. The β-alkylidenesuccinanilic acids on treatment with cyanuric chloride in the presence of triethylamine gave the corresponding β-alkylisomaleimides in 78-80% yields via the β-alkylideneisosuccinimides with the exocyclic to endocyclic carbon-carbon double bond migration. The kinetically controlled products alkylisomaleimides in refluxing acetic acid furnished the thermodynamically controlled alkylmaleimides in 98% yield. The Wittig condensation of alkyl substituted isomaleimides/maleimides with aliphatic aldehydes gave the desired dialkyl substituted maleimides in high yields. A conversion of α-methylenesuccinanilic acids to α-methylisomaleimides has also been described, with 90% yield.     

O-Arylsulfonyl hydroxylamines via a decarboxylative rearrangement

(E)-O-Arylsulfonyl-N-(2-nitroalk-2-enyl)hydroxylamines were easily obtained in good yields starting from (E)-nitro allylic alcohols, the crucial step being an inorganic base-catalyzed decarboxylative rearrangement of proposed labile unsaturated carbamates. A possible mechanism for the outcome of the reaction, characterized by the unusual retention of the sulfonyloxy group, is proposed.     

A facile and stereoselective synthetic method for allylic 1,3-dienyl ethers

The 1,4-elimination reaction of 1-allyloxy-4-methoxy-(2Z)-alkenes with n-butyllithium is shown to proceed in a marked preference to the [2,3] Wittig rearrangement to afford the allylic (1Z,3E)-dienyl ethers in high stereoselectivities. The synthetic utility of this method is demonstrated by the Claisen rearrangement of the dienyl ethers thus obtained.     

Enantioselective synthesis of lyxo-(2R,3R,4R)-C18-phytosphingosine using double stereodifferentiation

lyxo-C₁₈-Phytosphingosine can be synthesized by the cis-dihydroxylation of an (E)-allylic trichloroacetamide obtained by an Overman rearrangement. A double stereodifferentiation using AD-mix-β and an enantiomerically enriched (S)-allylic trichloroacetamide allowed the first synthesis of lyxo-(2R,3R,4R)-C₁₈-phytosphingosine with high diastereoselectivity (de=94%) and excellent enantioselectivity (ee=93%). This sphingosine was fully characterized by the physical and spectral data of the corresponding tetraacetate.     

Novel sequence of two base-catalyzed 1,3 proton shifts and [1,2] Wittig rearrangement in the synthesis of 2,4-bis-(trifluoromethyl)-6-phenylpyridine

The reaction of 1,1,1,5,5,5-hexafluoro-2,4-pentanedione with (R)-phenylglycinol was found to proceed via intermediate formation of (R, 4E, 6Z)-5,7-bis-(trifluoromethyl)-2,3-dihydro-3-phenyl-1,4-oxazepine which further underwent a base-catalyzed 1,3-proton shift reaction followed by [1,2] Wittig rearrangement giving rise to 2,4-bis-(trifluoromethyl)-6-phenylpyridine.     

An efficient synthetic route to chiral 4-alkyl-1,2,3,4-tetrahydroquinolines: enantioselective synthesis of (R)-4-ethyl-1,2,3,4-tetrahydroquinoline

An efficient synthetic route to non-racemic chiral 4-alkyl-1,2,3,4-tetrahydroquinoline is described. (4R)-4-Ethyl-1,2,3,4-tetrahydroquinoline was obtained by the organoaluminum promoted modified Beckmann rearrangement involving the oxime sulfonate of (3R)-3-ethylindan-1-one. The required optically active indanone was obtained via an asymmetric conjugate reduction of (E)-ethyl 3-phenylpent-2-enoate.     

Synthesis and oxidation of (E)-1,2-diphenyl-2-(arylimino) ethanol derivatives

The compounds (E)-1,2-diphenyl-2-(phenylimino)ethanol, (E)-1,2-diphenyl-2-(p-tolylimino)ethanol, and (E)-2-((4-chlorophenyl)imino)-1,2-diphenylethanol) were synthesized by reaction of a p-substituted aniline with benzoin then oxidized with chromium trioxide–triethylamine in chloroform to give (E)-1,2-diphenyl-2-(phenylimino)ethanone, (E)-1,2-diphenyl-2-(p-tolylimino)ethanone, and (E)-2-((4-chlorophenyl)imino)-1,2-diphenylethanone in very high yield. The products were characterized by IR and NMR spectral analysis.     

Syntheses and Mass Spectral Studies of (E)-1-Alkanesulfonylpropenes and (E)-1-Alkanesulfinylpropenes

(E)-1-Alkanesulfonylpropenes and (E)-1-Alkanesulfinylpropenes have been synthesized in good to excellent yields. Studies correlating molecular structure and fragmentation patterns upon electron impact have been carried out. Double hydrogen rearrangements with the elimination of alkenyl radicals are the most facile fragmentations for (E)-1-alkanesulfonylpropenes. Single hydrogen rearrangement with alkene elemination is however the most important fragmentation for (E)-1-alkanesulfinylpropenes. In this case the hydrogen atom only migrates to the sulfinyl oxygen. These differences in fragmentation patterns between the (E)-styryl-alkyl-sulfones/sulfoxides and the (E)-propenyl-alkyl-sulfones/sulfoxides are attributed to the fact that different ionization sites are involved.     

Regioselective biocatalytic hydrolysis of (E,Z)-2-methyl-2-butenenitrile for production of (E)-2-methyl-2-butenoic acid

Acidovorax facilis 72W nitrilase catalyzed the regioselective hydrolysis of (E,Z)-2-methyl-2-butenenitrile, producing only (E)-2-methyl-2-butenoic acid with no detectable conversion of (Z)-2-methyl-2-butenenitrile. (E)-2-Methyl-2-butenoic acid, produced in aqueous solution as the ammonium salt, was readily separated from (Z)-2-methyl-2-butenenitrile, and isolated in high yield and purity. The combination of nitrile hydratase and amidase activities of several Comamonas testosteroni strains were also highly regioselective for the production of (E)-2-methyl-2-butenoic acid from (E,Z)-2-methyl-2-butenenitrile.     

Synthesis and reactions of 3-(3-ethoxycarbonyl-1-phenyl-1<Emphasis Type="Italic">H</Emphasis>-pyrazol-4-yl)propenic acid

The reaction of ethyl 4-formyl-1-phenyl-1H-pyrazole-3-carboxylate with the malonic acid led to the formation (2E)-3-(3-ethoxycarbonyl-1-phenyl-1H-pyrazol-4-yl)propenic acid. In reactions of this acid chloride with 4-amino-5-aryl(hetaryl)-4H-1,2,4-triazole-3-thiols were obtained ethyl 4-[(E)-2-{3-aryl(hetaryl)[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-6-yl}ethenyl]-1-phenyl-1H-pyrazoe-3-carboxylates, with 5-aryltetrazoles, ethyl 4-[(E)-2-(5-aryl-1,3,4-oxadiazol-2-yl)-ethenyl]-1-phenyl-1H-pyrazole-3-carboxylates, with 1-(2-hydroxy-3,5-dimethylphenyl) followed by the Baker-Venkataraman rearrangement and the cyclization, ethyl 4-[(E)-2-(6,8-dimethyl-4-oxo-4Hchromen-2-yl)ethenyl]-1-phenyl-1H-pyrazole-3-carboxylate.     

Wittig rearrangement of 1-[(1E)-3-(Benzyloxy)prop-1-en-1-yl]adamantane

Wittig rearrangement of an allyl benzyl ether containing an adamantane fragment has been studied. 1-[(1E)-3-(Benzyloxy)prop-1-en-1-yl]adamantane reacts with butyllithium to give [2,3]- and [1,2]-rearrangement products. The [2,3]-rearrangement product is a mixture of threo and erythro diastereoisomers, the latter prevailing.