E. P. Serebryakov

The effects of the nature of catalyst and of the solvent on the stereoselectivity in amine-catalyzed asymmetric synthesis of substituted cyclohexa-1,3-dienes from prenal and monoesters of ylidenemalonic acids

In the amine-catalyzed reactions of prenal with (Z)-5-methyl-2-(methoxycarbonyl)hexa-2,4-dienoic or (Z)-3-phenyl-2-(ethoxycarbonyl)prop-2-enoic acid chiral β-amino alcohols provide for higher enantiomeric purity of the resulting alkyl 4-methyl-6-(2-methylprop-1-enyl)-and 4-methyl-6-phenylcyclohexa-1,3-dienoates than that provided by related chiral amines without hydroxy group. The values ofee attained in nonpolar solvents are higher than those observed in the polar ones. Substituting stoichiometric amounts of a chiral 1-amino-3-methylbuta-1,3-diene for a combination of prenal with 0.1 equiv. of the corresponding chiral amine results in the products of much lower enantiomeric purity.

A versatile and convenient protocol for the stereocontrolled synthesis of olefinic insect pheromones

A combination of the Horner-Emmons synthesis of alkyl 2,4-dienoates with their hydrogenation over complex L.Cr(CO)3 catalysts (L = 3CO or arene) provides a versatile, stereocontrolled and operationally simple approach to the (Z)-disubstituted, (Z)-trisubstituted, (E)-trisubstituted alkenes and skipped (Z,Z)-disubstituted diolefins with a homoallylic type of functionally. This protocol, sometimes supplemented by an enzymatic hydrolysis, was successfully applied to the synthesis of configurationally pure (gp > or = 98%) pheromones of the furniture carpet beetle, dry bean beetle, rusty grain beetle, square-necked grain beetle and a trail-following pheromone mimic for subterranean termites.

Regio- and stereoselectivity in the addition reactions of CH-acids to aldehydes under the conditions of phase-transfer catalysis

The regio- and stereoselectivity of the reactions of carbanions, generated from alkanals, carboxylates of the type XYCHCOOEt (X = EtOOC, CN, Ac; Y = H, Br), or derivatives of 3-methyl-4-phosphono-2-butenoic acid using PTC techniques, with aldehydes of various types (alkanals, α,β-enals, cross-conjugated enedials, benzaldehydes,etc.) are reviewed. The factors affecting the outcome of these reactions are discussed. The carbanion analogs, triphenylphosphorus ylides, are shown to attack selectively at one of the aldehyde groups of aromatic dialdehydes. The regularities found for the title reactions were used in the syntheses of some biologically active isoprenoids.

Synthesis of polysubstituted 1,3-cyclohexadienes from β-branched α,β-alkenals and monoesters of ylidenemalonic acids

Abstract3-Methyl- and 3-phenyl-2-butenal react with monoesters of alkylidene-, alkenylidene-, and arylmethylenemalonic acids in the presence of piperidine as the catalyst to give esters of 4,6-disubstituted 1,3-cyclohexadienecarboxylic acids in 23–96% yields. Under the same conditions cyclohexylideneacetic aldehyde reacts with the monoesters of prenylidene- and benzylidenemalonic acid to afford mixtures of 1,8a-trans- and 1,8a-cis-isomers of 1-substituted alkyl 1,5,6,7,8,8a-hexahydronaphthalene-2-carboxylates, the ratios and configurations of which were determined by means of1H NMR spectroscopy. In some cases the formation of cyclic dienes is impeded by the competing process of decarboxylation of acidic ylidenemalonates. The derivatives of 4,6-diphenyl-1,3-cyclohexadienecarboxylic acid were shown to be convenient precursors for the preparation ofmeta-terphenyls.

Catalytic asymmetric synthesis of polysubstituted cyclohexa-1,3-dienes from β-branched α,β-alkenals

Abstract3-Methyl- and 3-phenylbut-2-enal in the presence of (S)-prolinol (0.1 eq.) in benzene or THF react with the acidic monoesters of alkenylidene, and arylmethylidene-, and alkylidenemalonic acids at −10 to +22 °C to give optically active esters of 4,6-disubstituted cyclohexa-1,3-diene-l-carboxylic acids in moderate (10–43 %) yields. The enantiomeric purity of the products formed from the lint two types of acidic ylidenemalonates varies from 28 to 68 % and is higher than that observed in the case of related alkylidenemalonates. Under similar conditions cyclohexylideneacetaldehyde affords optically active derivatives of 1,5,6,7,8,8a-hexahydronaphthalene as mixtures ofcis andtrans isomers. The enantiomeric purity and absolute configuration of the cyclohexadienes thus obtained were determined using1H NMR spectroscopy in combination with chiral solvating agents.

Stereospecific 1,4-cis-hydrogenation of conjugated dienes, dienynes, and dienediynes catalyzed by chromium carbonyl complexes in stereocontrolled syntheses of physiologically active olefins

Synthesis of insect pheromones provides a good illustration of versatility, flexiblility, and practical convenience of the chromium carbonyl complexes-mediated 1,4-cis-hydrogenation of conjugated dienes as the tool for for stereocontrolled construction of di-, tri-, and tetrasubstituted olefins and nonconjugated dienes. A new strategy for synthesizing homoconjugated all-Z-dienes and trienes by hydrogenation of diene-alkyne conjugated systems using the same catalysts is proposed.

Enantioselectivity of enzymatic acylation of some structurally various racemic alcohols in anhydrous aprotic media

Partial acylation of (R,S)-3,7-dimethyloctan-1-ol (1) and (R,S)-7-methoxy-3,7-dimethyloctan-1-ol (2) with vinyl acetate catalyzed by the lipase fromCandida cylindracea affords in good yields the correspondingS-configured acetates with 92–98% enantiomeric excess (ee). Under similar conditions, racemic α-cyclogeraniol (3), drim-7-en-11-ol, methyl 4-(3-hydroxy-2-methylpropyl)benzoate, and its η6-chromium(tricarbonyl) complex (6) are acylated with rather poor (and, for the two latter, opposite) enantioselectivity, whereas (R,S)-2,4∶3,5-di-O-benzylidenexylitol remains unaffected. Racemic isoborneol (8) and 2-nitro-1-phenylethanol also remain almost or completely unconverted. Attempts to perform enantioselective acylation of alcohols 3 and 8 with Ac2O in the presence of porcine pancreatic lipase (PPL) proved equally unsuccessful. By contrast, the PPL-catalyzed acylation of alcohol 6 with vinyl acetate at 17% conversion affords the levorotatory acetate (S)-6a withca. 100%ee. PPL-Mediated partial acylation of (R,S)-pantolactone with Ac2O, followed by mild deacylation of the resultingR acetate, gives (R)-(-)-pantolactone of 97% enantiomeric purity in 60% overall yield.

Lipase-mediated deracemization of secondary 1-phenyl-substituted propargylic alcohols of different topology

Acetylation of (±)-1-phenylnon-2-yn-1-ol, (±)-1-phenylhept-1-yn-3-ol, and (±)-1-phenylundec-4-yn-3-ol ((±)-5) in the presence of lipase from Candida cylindracea (CCL) proceeds slowly to give products with ee ≤20%. The acetates of these alcohols are hydrolyzed in the presence of porcine pancreatic lipase (PPL) equally unsatisfactorily. The (η6-arene)tricarbonylchromium complex of alcohol (±)-5 is acetylated in the presence of CCL up to ∼22% conversion to give (R)-acetate whose oxidative decomplexation followed by saponification results in alcohol (R)-(–)-5 with ee ≥95%. The configuration of alcohols (–)-5 and (+)-5 was determined by NMR spectroscopy of their esters with (R)- and (S)-Moshers acids.

2,5,6,7,8-Pentasubstituted (S)- and (R)-[2-chroman-2-yl]ethanols as intermediates for the synthesis of α-tocopherol and its chiral analogs

In the presence of lipase from the yeast Candida cylindracea, partial acetylation of (±)-2-[6-benzyloxy-2,5,7,8-tetramethylchroman-2-yl]ethanol with vinyl acetate gives S-(+)-acetate whose alkaline hydrolysis affords (S)-(–)-alcohol. Repeated enzymatic acetylation of the “residual” alcohol up to ∼39% conversion afforded the R-enantiomer. The enantiomeric alcohols were oxidized to (S)- or (R)-aldehydes having the same sign of [α]D as the original alcohols. These alcohols were converted into S-(+)- and R-(–)-enantiomers of the antioxidant MDL-73404, a hydrophilic analog of α-tocopherol.

Lipase-mediated ‘meso-tricks’ to transform latently symmetrical d-aldoses into l-aldoses via alditols

Abstract l -Fucose and l -xylose were synthesized from dulcitol and xylitol, respectively, using CCL- or PPL-mediated kinetic resolution as the key step. In the first case dissymmetrization was achieved directly by acylating a meso derivative, while in the second it was preceded by the conversion of the meso polyol into a racemic intermediate.