Reactivity of aldehydes with semi-stabilised arsonium ylide anions: synthesis of terminal (e)-1,3-dienes

A study of the reactivity of semi-stabilised arsonium ylide anions in olefination reactions is presented. The different ylide anions were generated by the addition of nBuLi to various arsonium halide derivatives: [Ph(2)As(R)R'](+)X(-), where R and R' are methyl, allyl, prenyl or benzyl groups. By using diallyldiphenylarsonium bromide (R=R'=allyl) an olefination protocol was optimised allowing the efficient transformation of aliphatic aldehydes into terminal 1,3-dienes with a high selectivity for the E isomer (E/Z ratios ranging from 90:10 to 97:3). The olefination reactions of aldehydes with dissymmetric arsonium halides (R not equal R') are very chemoselective; with arsonium ylide anions the benzyl moiety is more reactive than the allyl moiety which is much more reactive than prenyl and methyl groups. Based on the experimental results, a mechanism is proposed for the reaction.     

A highly stereoselective route to substituted bis-tetrahydrofurans from 1,5-dienes.

Bis-tetrahydrofurans $\text{1a}$ and $\text{1b}$, containing four chiral centers, are obtained with a 90 % isomeric purity from geranyl and neryl chlorides in four steps including two stereoselective cyclizations.     

γ-Trimethylsilyl-substituted allylzirconcenes in organic synthesis. Stereoselective synthesis of terminal 1,3-butadienes and functionalized vinylsilanes

γ-Trimethylsilyl-substituted allylzirconcenes, prepared by hydrozirconation of trimethylsilyl-substituted terminal allenes, react with aldehydes at the γ-position to give 1,3-butadienes in one step with good stereoselectivity and undergo conjugate addition to α,β-unsaturated aromatic ketones at the α-position to selectively afford functionalized vinylsilanes in the presence of catalytic CuBr·SMe₂.     

Multi-component, 1,3-dipolar cycloaddition reactions for the chemo-, regio- and stereoselective synthesis of novel hybrid spiroheterocycles in ionic liquid

A library of novel 1-methyl-4-arylpyrrolo-(spiro[2.2′]indan-1′,3′-dione)-spiro[3.3″]-1″-methyl/benzyl-5″-(arylmethylidene)piperidin-4″-ones and 1-methyl-4-arylpyrrolo-(spiro[2.11′]-11H-indeno[1,2-b]quinoxaline)-spiro[3.3″]-1″-methyl/benzyl-5″-(arylmethylidene)piperidin-4″-ones have been synthesized via 1,3-dipolar azomethine ylide cycloaddition in the ionic liquid, 1-butyl-3-methylimidazolium bromide ([BMIm]Br), in excellent yields.     

A novel access to highly functionalised β-lactams by regio- and stereoselective 1,3-dipolar cycloaddition reaction

A highly regio- and stereoselective synthesis of novel spiro pyrrolidines/pyrrolizidines containing β-lactam and oxazolone moieties under two different conditions is achieved using [3+2] cycloaddition methodology in moderate to good yield.     

A double regio- and stereoselective glycosylation strategy for the synthesis of N-glycans

A building block approach for biantennary N-linked oligosaccharides from glycoproteins (N-glycans) has been developed. Starting from a core trisaccharide (beta-mannosyl chitobiose) containing a benzylidene-protected beta-mannoside, the attachment of the disaccharide building blocks for the antennae can be performed in a double regio- and stereoselective manner. A short synthesis of a GlcNPhtbeta1,2Man donor was developed. The benzylidene acetal moiety, as a minimal protection of the beta-mannoside, allows selective alpha-glycosylation at OH-3 of the 2,3-diol with GlcNbeta1,2Man trichloroacetimidate donors. Subsequent debenzylidenation leads to a 4,6-diol, which can be selectively extended at OH-6. Overreaction at OH-4 was generally low when phthalimido-protected donors were used. This general strategy represents a modular synthesis of N-glycans and their glycoconjugates.     

Chemo-, regio- and stereoselective 1,3-dipolar cycloaddition of C-aryl-N-phenylnitrones over 3,5-bis(arylidene)-1-methylpiperidin-4-ones: synthesis of highly substituted novel spiro-isoxazolidines

1,3-Dipolar cycloaddition of C-aryl-N-phenylnitrones to 3,5-bis-(arylidene)-1-methylpiperidin-4-ones affords novel mono- and bis-spiroisoxazolidines in moderate yields. In general, this reaction predominantly yields mono-spiroisoxazolidine, wherein the oxygen of the nitrone is linked to the β-carbon of the benzylidene moiety, while 3,5-bis-(2-chloro- and 3-nitro-benzylidene)-1-methylpiperidin-4-ones afford predominantly bis-spiroisoxazolidines. The cycloaddition of mono-spiroisoxazolidines occurs with facial diastereoselectivity to furnish bis-spiroisoxazolidines. The nitrogen in the heterocyclic ring of the 3,5-bis-(arylidene)-1-methylpiperidin-4-ones facilitates the cycloaddition through transannular (NCO) and/or homoconjugative (NCC) interactions.     

1,3-Dipolar cycloadditions of nonstabilized azomethine ylides to planar chalcones via regio- and stereoselective route: A three-component strategy

Simple and efficient strategies toward the synthesis of trisubstituted pyrrolizidines and disubstituted oxazolidine systems by 1,3-dipolar cycloaddition reactions using arylaldehydes and α-amino acids have been developed, followed by a one-pot, three-component strategy. Electron-deficient dipolarophiles, chalcones, were reacted with nonstabilized azomethine ylides derived from arylaldehyde and L-proline in dry dimethyl formamide, leading to substituted pyrrolizidines. The route to substituted oxazolidines involved cycloaddition to the C?O bond of a second molecule of the aldehyde. The structures and stereochemistry of the cycloadducts were established by infrared (IR), NMR spectroscopy, and single-crystal x-ray crystallographic analyses. Condensed Fukui functions and local electrophilicity indices have been computed to characterize the reactive sites and predict the preferred interactions of azomethine ylides to planar chalcones. The softness-matching indices have been evaluated to determine the regioselectivity of the cycloaddition reactions. The theoretical predictions were found to be in complete agreement with the experimental results, implying that the density functional theory (DFT)-based reactivity indices correctly predict the regioselectivities of 1,3-dipolar cycloadditions of azomethine ylides to planar chalcones. The frontier molecular orbital (FMO) energies, electronic chemical potentials, chemical hardness, chemical softness, and global electrophilicity indices of azomethine ylides have been calculated at the DFT/B3LYP/6-31 + G (d, p) level of theory.     

Stannes in synthesis: A new route to 2-substituted-1,3-butadienes via stereoselective allyltin formation under homolytic conditions

α-(Hydroxymethyl) allyl tolylsulfones reacted with tributyltin hydride in the presence of azobisisobutyronitrile (AIBN) in refluxing benzene to give a allyltin derivatives which subsequently gave 2-substituted1,3-butadienes upon distillation in good yield.     

A convenient one-pot synthesis of homoallylic halides and 1,3-butadienes

An efficient one-pot synthetic pathway for the preparation of homoallylic halides by in situ generated MgBrCl-promoted ring opening of cyclopropylcarbinyl acetates has been established. An easily accessible one-pot synthetic protocol of 1,3-butadienes by the elimination of hydrogen halides from the resulting homoallylic halides in the presence of an excess amount of strong base has also been developed.     

A novel route to substituted 3-methylidenechroman-2-ones and 3-methylchromen-2-ones

3-Methylidenechroman-2-ones, or their rearrangement products 3-methylchromen-2-ones, were efficiently synthesized by Michael addition of various nucleophiles to 3-diethoxyphosphorylchromen-2-ones followed by Horner-Wadsworth-Emmons reaction of the adducts with formaldehyde. Relative configuration and conformation of the intermediate adducts were studied using NMR spectroscopy and semiempirical PM3 calculations.     

1,3-Diphenylpropane-1,3-diamines,X: Synthesis and biochemical evaluation of highly substituted 1,3-diphenylpropane-1,3-diamines and preparation of their Pt(II) complexes

Summary The ligands of the title complexes1 and2 were prepared from the pertinent chalcone5 and hydrazine hydrate, followed by N-N cleavage. The estrogenic activity of the diamines11 and12 was determined by measuring the RBA values (calf uterine cytosol) and by a luciferase test in MCF 7-2a cells. The compounds are by far less active thanSchönenberger's most active compound ([meso-1,2-bis(2,6-dichloro-4-hydroxyphenyl)ethane-1,2-diamine]dichloro-platinum(II),3).Dedicated with kind regards to Prof. Dr.G. Seitz, Marburg/Germany, on the occasion of his 60^th birthday     

Thiourea to bicyclic scaffolds: highly regio- and stereoselective routes to dithiazolopyrimidines

Microwave-activated solvent-free Michael addition of 3-imino-1,4,2-dithiazoles to 4-arylidene-5(4H)-oxazolones furnished isolable adducts regio- and diastereoselectively, which underwent ring transformation to yield the target dithiazolopyrimidines. Alternatively, the similar conjugate addition of methanesulfinylmethylisothioureas to 4-arylidene-5(4H)-oxazolones diastereoselectively afforded Michael adducts, which underwent ring transformation followed by heterocyclization via deoxygenative demethylation with thionyl chloride to yield the same products dithiazolopyrimidines regio- and diastereoselectively.