Stereoselective synthesis of 2-(α-hydroxyalkyl)benzimidazoles

Lithiated oxazolo[3,4-a]benzimidazole 4 reacted with various alkyl halides to give oxazolo[3,4-a]benzimidazoles 5a–d in good yields as single diastereoisomers. (R)-Benzimidazol-2-yl carbinols 6a–d were obtained upon hydrolysis under acidic conditions of 1H,3H-oxazolo[3,4-a]benzimidazole derivatives.     

Photooxidations of 2-(γ,ε-dihydroxyalkyl) furans in water: synthesis of DE-bicycles of the pectenotoxins

Photooxygenations of 2-(γ,ε-dihydroxyalkyl) furans in H(2)O followed by in situ reduction and ketalization affords, in one synthetic operation, DE-bicyclic ketals of the pectenotoxins.     

Stereoselective synthesis of 3-(ω-hydroxyalkyl)-2-pyrrolidinones from α-alkylidenelactones and nitromethane

Enantiopure 3-(ω-hydroxyalkyl)-2-pyrrolidinones 7 and 9 were synthesised by Michael-addition of nitromethane to chiral α-alkylidenelactones 1 followed by reduction of the resulting 3-(β-nitroalkyl)-lactones and ring transformation of the intermediate 3-(β-aminoalkyl)-lactones. In an analogous manner the naturally occurring costuslactone 10 was transformed into the butyrolactam 12.     

Enantioselective synthesis of (S)- and (R)-α-methylserines: application to the synthesis of (S)- and (R)-N-Boc-N,O-isopropylidene-α-methylserinals

This report describes the synthesis of enantiomerically pure (S)- and (R)-α-methylserines on a multigram scale, starting from the Weinreb amide of 2-methyl-2-propenoic acid and using a stereodivergent synthetic route that involves a Sharpless asymmetric dihydroxylation reaction. As a synthetic application of these quaternary α-amino acids, they were used as starting materials in the synthesis of the well-known valuable homochiral (S)- and (R)-N-Boc-N,O-isopropylidene-α-methylserinal building blocks.     

α-hydroaxyalkyl(benzyl)furozans and α-hydroxyalkyl(benzyl)furoxans synthesis and reactivity

A general and simple preparative method for the synthesis of -hydroxyalky(benzyl)furazan and -furoxan derivatives is proposed, The method involves reduction of acyl or ethoxycarbonyl substituents in these heterocyclic compounds with NaBH₄ in ethanol. Based on the alcohols thus prepared, a number of previously unknown functional derivatives (-nitroxyalkyl--haloalkyl-, and -azidoalkylfurazans and -furoxans) have been synthesized.Translated fromInvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7. pp, 1782–1788, July, 1996.     

Functionalized 3(2H)-furanones via photooxygenation of (β-keto)-2-substituted furans: application to the biomimetic synthesis of merrekentrone C

Photooxygenation of (β-keto)-2-substituted furans leads, in a one pot operation, to functionalized 3(2H)-furanones with good to excellent yields. This methodology was applied as a key-step to the concise and biomimetic synthesis of the sesquiterpene merrekentrone C. The precursor to merrekentrone C, keto difuran, was synthesized using a cross coupling of α-iodo-3-acetylfuran with an alkenyl furan under Fenton-type conditions.     

An efficient microwave assisted synthesis of N′-aryl/(alkyl)-substituted N-(4-hydroxy-6-phenylpyrimidin-2-yl)guanidines: Scope and limitations

Treatment of N-[(4-hydroxy-6-phenyl)pyrimidin-2-yl]cyanamide with 1° alkyl or arylamines in isopropyl alcohol for only 10 min at 110–120 °C under microwave conditions gave the corresponding N′-alkyl(aryl)guanidine derivatives in excellent yields (65–84%). Isolated yields were greatest when >1.0 equiv. of amines were employed, but excellent results were also obtained when aryl and alkylamines were reacted with a more atom-economical loading (1.0 equiv.; 70% and 72% ave. yields, respectively). Arylamines with either highly electron withdrawing substituents (e.g. CO₂H) or pi-deficient heterocycles (e.g. variously substituted aminopyridines) did not work well under these conditions, and reaction with ureas and/or amino acids did not give detectable products. Work-up was exceedingly simple, and involved simple collection and washing of product on a sintered glass funnel. Products were obtained in analytically pure form and required approximately 1 h to prepare, start to finish.     

Tris-ACE-(6,6′-bipyridyl)-α-cyclodextrin: synthesis and chirality of the tripodal metal complexes

This Letter describes the synthesis of a C₃-symmetrical tris-^ACE-(6,6′-bipyridyl)-α-CyD via ‘one-pot’ Staudinger-Aza-Wittig reaction (SAW). Metal complexation behavior was investigated by UV–vis and Circular Dichroism. Coordination of 6,6′-bipyridyl units with Cu^II and Ni^II cations, spontaneously generates a strong exciton coupling-type positive Cotton effect proving the formation of a Λ-helix with a left-handed screw propeller (M).     

Synthetic studies towards(-)-deserpidine:Total synthesis of the stereoisomer and derivative of (-)-deserpidine

The asymmetric synthesis of 16,17,20-epi-deserpidine and a derivative of(-)-deserpidine has been achieved.Key feature s in the assembly of the pentacyclic framework include a visible-light photocatalytic intra-/inter-/intramolecular radical cascade reaction to construct the tetracyclic ABCD ring system in one-pot and an intramolecularaldol reaction to forge the cyclohexane E ring.     

A continuous-flow synthesis of annulated and polysubstituted furans from the reaction of ketones and α-haloketones

A synthesis of di-, tri- and tetra-substituted furans from reaction of the corresponding ketones and α-haloketones with LiHMDS is reported. Reaction under continuous-flow conditions gave increased yields and removed the need for external cooling when compared to the unoptimised batch conditions.     

Modular synthesis of 1-α- and 1-β-(indol-2-yl)-2'-deoxyribose C-nucleosides

A simple two-step method for the selective preparation of anomerically pure 1α- and 1β-(indol-2-yl)deoxyribose derivatives was developed. The synthesis was based on the Sonogashira reaction of 1α- and 1β-ethynyldeoxyribose and 2-haloanilines followed by a Pd-complex catalyzed cyclization to the corresponding indolyldeoxyribosides.     

Total synthesis of 2-(2-hydroxyalkyl)-piperidine alkaloids (−)-halosaline and (−)-8-epi-halosaline via iterative asymmetric allylation/RCM strategy

Total synthesis of 2-(2-hydroxyalkyl)-piperidine alkaloids, (?)-halosaline and (?)-8-epi-halosaline is reported from n-butyraldehyde using iterative asymmetric allylation, nucleophilic substitution with an azide and ring-closing metathesis as the key reactions.     

Metallation of benzyl selenides and of α-aryl selenoacetals. Scope and limitations.

α-Metallo benzylselenides and α-metallo selenoacetals derived from aromatic aldehydes have been conveniently prepared by metallation of the corresponding carbon acids. KDA in THF proved among the various basic systems tested, the most efficient.α-Metallo benzylselenides and α-metallo selenoacetals derived from aromatic aldehydes have been conveniently prepared by metallation with KDA of the corresponding carbon acids. These reactions have been used for the synthesis of arylalkanes, including those bearing a trialkylated benzylic carbon, from aromatic aldehydes.     

Conjugate addition of lithium N-phenyl-N-(α-methylbenzyl)amide: application to the asymmetric synthesis of (R)-(-)-angustureine

The conjugate addition of lithium (R)-N-phenyl-N-(α-methylbenzyl)amide to a range of α,β-unsaturated 4-methoxyphenyl esters proceeds with excellent levels of diastereoselectivity to give the corresponding β-amino esters in good yield and as single diastereoisomers (>99:1 dr). The synthetic utility of this methodology has been demonstrated via the short and concise asymmetric synthesis of the tetrahydroquinoline alkaloid (R)-(-)-angustureine in six steps and 32% overall yield from commercially available oct-2-enoic acid.     

The synthesis of (R)- and (S)-α-trifluoromethyl-α-hydroxycarboxylic acids via enzymatic resolutions

Kinetic resolution of 1,1,1-trifluoro-2-alkanone cyanohydrin acyl derivatives with Candida rugosa lipase afforded the remaining (R)-enantiomer in high selectivity (E from 30 to >200). Candida rugosa lipases from several suppliers were compared and found to differ remarkably in their selectivity. The (R)-enantiomer was hydrolyzed in one step to yield optically pure (R)-α-trifluoromethyl-α-hydroxycarboxylic acids in excellent yield. The (S)-acids were obtained in good e.e. by subtilisin-catalyzed resolution of the corresponding racemic esters followed by chemical hydrolysis of the remaining (S)-esters.     

Asymmetric synthesis of (S)- and (R)-α-methylserine based on the chiral recyclable reagent (S)-N-(2-benzoyl-phenyl)-1-benzylpyrrolidine-2-carboxamide

Both enantiomers of -methylserine were synthesized with the use of Ni^II complexes based on the chiral recyclable reagent (S)-N-(2-benzoylphenyl)-1-benzylpyrrolidine-2-carboxamide. Intermediate diastereomeric complexes were separated by crystallization of their O-acetyl derivatives.     

β-Hydroxy-α-tosyloxy esters as chiral building blocks for the enantioselective synthesis of benzo-annulated oxa-heterocycles: scope and limitations

The enantioselective synthesis of benzo-annulated oxa-heterocycles 2,3-dihydrobenzofuran and 1-benzopyran derivatives is described using β-hydroxy-α-tosyloxy esters as chiral building blocks, which are easily accessible through the regioselective α-tosylation of Sharpless asymmetric dihydroxylation-derived syn-2,3-dihydroxy esters.     

Enantioselective synthesis of (S)- and (R)-6-hydroxy-8-nonene-carboxylates by asymmetric catalysis: a formal synthesis of (R)-α-lipoic acid and its (S)-antipode

A short and efficient enantioselective synthesis of (S)- and (R)-configured 6-hydroxy-8-nonene-carboxylates — precursors to (R)-α-lipoic acid and its (S)-enantiomer — by allylation of alkoxycarbonyl substituted aldehydes with allyltrimethylstannane and BINOL/Ti(OiPr)₄ catalyst is described. The best results in terms of enantiomeric purity and yield are obtained employing 10 mol% of the titanium-species without molecular sieves.     

Exploring the metal-catalyzed reaction of furans with alkyl α-diazomethanesulfonate and α-diazomethanephosphonate: synthesis of ω-acyl-substituted sulfono- and phosphonobutadienes

The metal-catalyzed reactions of neopentyl α-diazomethanesulfonate (DAMS) and diisopropyl α-diazomethanephosphonate (DIDAMP) with furan, 2-methylfuran and 2-methoxyfuran are reported. The products consist mostly of ω-acyl-substituted sulfono- or phosphonobutadienes and exo-cyclopropane derivatives. Treatment of the multicomponent reaction mixtures with iodine afforded exclusively the corresponding (E,E)-sulfono- and phosphono-ω-acylfunctionalized dienes, thus providing a short and efficient synthetic route to these hitherto unreported classes of compounds.