Synthesis of highly substituted tetrahydropyrans: preparation of the C20-C28 moiety of phorboxazoles

A propionate-derived polyketide building block A whose 2-methyl-1,3-diol moiety was built by a Ti(III)-mediated ring opening reaction of a trisubstituted 2,3-epoxy alcohol precursor was employed as a common starting material for the syntheses of highly substituted tetrahydropyrans 1-5, the first one being the C20-C28 fragment of cytotoxic natural products, phorboxazoles.     

Regioselective nucleophilic ring-opening reaction of chiral epoxyallyl alcohols: a ready access to the pyran core of macrolactin 3

Herein we report the synthetic strategy towards the pyran core of macrolactin 3 via Sharpless epoxidation, titanium(IV) mediated regioselective ring-opening reaction of epoxyallyl alcohol/epoxy alcohol and oxa-Michael addition as the key steps.     

Stereoselective construction of quaternary chiral centers using Ti(III)-mediated opening of 2,3-epoxy alcohols: studies directed toward the synthesis of penifulvins

A trisubstituted α,β-unsaturated ester moiety was suitably placed in a molecule also bearing an epoxy alcohol moiety at its other end to intramolecularly trap the intermediate radical, which was formed when the molecule was treated with Cp₂Ti(III)Cl to regio- and stereoselectively open its epoxy ring, giving rise to a quaternary chiral center. The method was subsequently used in an attempt to construct the bicyclic core framework of potent insecticides penifulvins.     

Polymer bromide-DMSO: novel reagent system for the oxidation of alcohols to carbonyl compounds

A novel method for the oxidation of alcohols to aldehydes is described using polymer bromide-DMSO at room temperature. The condition described enables clean and fast conversion to desired carbonyl compounds and a broad range of substrates are tolerated. The resin recovery and recyclability make the protocol more ecofriendly.     

Studies on the synthesis of DNA-damaging part of leinamycin: regioselectivity in Ti(OiPr)4 mediated opening of hydroxy epoxides with carboxylic acids

The preparation of the key intermediate in the synthesis of the DNA damaging fragment of the anticancer antibiotic leinamycin starting from geraniol is described. The synthetic sequence involves the building of a quaternary asymmetric center through kinetic resolution through Sharpless epoxidation followed by the regioselective opening of the resultant enantiomerically pure hydroxyepoxide and intramolecular Wittig-Horner olefination.     

Facile and efficient synthesis of lactols by a domino reaction of 2,3-epoxy alcohols with a hypervalent iodine(III) reagent and its application to the synthesis of lactones and the asymmetric synthesis of (+)-tanikolide

The domino reaction of 2,3-epoxy-1-alcohol derivatives, namely tetrasubstituted 2,3-epoxy-1-alcohols and 2- or 3-alkyl trisubstituted 2,3-epoxy-1-alcohols, with PhI(OCOCF(3))(2) in the presence of H(2)O is described in detail. In this reaction, several types of lactol derivatives can be directly obtained from the 2,3-epoxy-1-alcohol derivatives in a single operation. The obtained lactols were successively converted into the corresponding lactones. This reaction is applicable to the construction of optically active lactone compounds. The asymmetric total synthesis of (+)-tanikolide, an antifungal marine natural product, has been effectively achieved by using this reaction.     

Reductive opening of glycal derived highly functionalized 2,3-epoxy-1-iodides with zinc dust: an efficient method for the synthesis of acyclic long chain polyhydroxylated terminal alkenic alcohols

The synthesis of densely functionalized acyclic long chain terminal alkenic alcohols was achieved by reductive opening of glycal derived 2,3-epoxy-1-iodides, with commercial zinc dust alone in a short reaction time with excellent yields involving a simple reaction procedure and easy work-up. A mechanism involving an organometallic intermediate is proposed.     

Efficient synthesis of carbonyl compounds: oxidation of azides and alcohols catalyzed by vanadium pentoxide in water using tert-butylhydroperoxide

Catalytic amount of vanadium reagent with tert-butylhydroperoxide as the oxidant was found to be an excellent oxidizing agent in aqueous medium. Vanadium pentoxide with aq tert-butylhydroperoxide readily oxidizes primary benzylic azides to the corresponding acids and secondary benzylic azides to the corresponding ketones in excellent yields. Further, vanadium pentoxide and aq tert-butylhydroperoxide combination turned out to be an effective catalyst for the oxidation of alcohols. Using vanadium pentoxide and aq tert-butylhydroperoxide primary alcohols were oxidized to the corresponding acids, whereas secondary alcohols underwent a smooth transformation to furnish corresponding ketones in excellent yields. All the oxidations are performed in water.     

Regio- and stereochemical aspects in the synthesis of homoallylic alcohols from benzoins and their iodocyclisation to 2,3-diphenyltetrahydrofurans

Indium mediated allylation, crotylation and cinnamylation of benzoins and its substituted derivatives in THF-H₂O (2/1) provide a range of homoallylic alcohols. In general, the benzoins undergo allylation and crotylation in a sluggish manner compared to those observed earlier in the case of α-hydroxy aldehydes and are significantly affected by the electronic features of both the benzoin and indium organometallic reagent. The reactions exhibit higher order of diastereoselectivities than those observed for α-hydroxy aldehydes. The cinnamylation though proceeds in a highly diastereoselective manner but is restricted to only benzoin and 4,4′-dichlorobenzoin. The homoallylic alcohols undergo I₂ mediated intramolecular diastereoselective cyclization to provide 2,3-diphenyltetrahydrofuran derivatives. The relative stereochemistries in tetrahydrofurans and homoallylic alcohols have been assigned by coupling constants, NOE experiments and in one case by X-ray crystallography.     

Kinetics and mechanism of catalytic oxidation of alcohols to carbonyl compounds with dioxygen in the Pd-containing aqua system

The oxidation of lower aliphatic alcohols C₁–C₄ with dioxygen to form the corresponding carbonyl compounds in the presence of the PdII tetraaqua complexes and Fe^II-Fe^III aqua ions in an aqueous medium was studied at 40–80 °C. The introduction of an aromatic compound (acetophenone, benzonitrile, phenylacetonitrile, o-cyanotoluene, nitrobenzene) and Fe^II aqua ion instead of the Fe^III aqua ion into the reaction system increases substantially the catalytic activity and the yield of the carbonyl compound. The key role of the Pd species in the intermediate oxidation state stabilized by the aromatic additive in the catalytic cycle of alcohol oxidation with dioxygen to the carbonyl compound was shown. An increase in the kinetic isotope effect with an increase in the temperature of methanol oxidation indicates a change in the rate-determining step of alcohol oxidation with dioxygen in the presence of Pd^II-Fe^II-Fe^III and the aromatic compound. At temperatures below 60 °C, the catalytically active palladium species are mainly formed upon the reduction of the Pd^II tetraaqua complex with the Fe^II aqua ion, whereas at higher temperatures the reaction between the alcohol and Pd^II predominates. The mechanism and kinetic equation of the process were proposed. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 842–848, May, 2007.     

Investigation of catalytic properties of two new orthopalladated complexes supported on montmorillonite: Synthesis,characterization and application in aerobic oxidation of alcohols

Two new complexes, [Pd(L₁)(C,N)]NO₃ ( 1 ) and [Pd(L₂)(C,N)]NO₃ ( 2 ) (L₁ = 5‐nitro‐1,10‐phenanthroline, L₂ = 4‐methyl‐1,10‐phenanthroline, C,N = benzylamine), have been synthesized and characterized using infrared and NMR spectroscopies and elemental analysis. Montmorillonite (MMT‐K10 clay) was used as a solid support for incorporating the cationic part of complexes 1 and 2 to produce catalysts 1 and 2 , respectively, as heterogeneous catalysts. Catalyst 1 was identified using powder X‐ray diffraction and scanning and transmission electron microscopies, and the content of palladium obtained from inductively coupled plasma analysis. By changing the electron‐donating group on the L₁ ligand with an electron‐withdrawing one, a minor improvement was observed in the catalytic properties. Catalyst 1 showed better efficiency for oxidation of benzyl alcohol in comparison with catalyst 2 , so catalyst 1 was used for the aerobic oxidation of alcohols to corresponding aldehydes or ketones without over‐oxidation (with and without bubbling of air). This catalytic system showed high activity towards alcohols under mild conditions. Finally, the reusability of catalyst 1 was investigated with multiple reuses of the supported catalyst in subsequent alcohol oxidation reactions.     

Green oxidation of alcohols by using hydrogen peroxide in water in the presence of magnetic Fe3O4 nanoparticles as recoverable catalyst

Magnetically nano Fe₃O₄ efficiently catalyzes green oxidation of primary and secondary benzylic and aliphatic alcohols to give the corresponding carbonyl products in good yields. The reactions were carried out in an aqueous medium in the presence of hydrogen peroxide as an oxidant at 50°C. In addition, the magnetically nano Fe₃O₄ catalyst could be reused up to four runs without any significant loss of activities. Catalyst was characterized by scanning electron microscopy, transmission electron microscopy, X-ray powder diffraction, thermogravimetric analysis, vibrating sample magnetometer, and IR.     

A new simple route to deoxyamino sugars from non-sugar material: synthesis of d-tolyposamine and 4-epi-d-tolyposamine and formal synthesis of d-vicenisamine

A new, simple strategy has been formulated for the synthesis of deoxyamino sugars from a non-sugar starting material. Starting from the enantiomerically pure diol obtained from ethyl sorbate by Sharpless asymmetric dihydroxylation, the synthesis of two types of 2,3,4,6-tetradeoxy-4-amino sugars—d-tolyposamine and 4-epi-d-tolyposamine—, and formal synthesis of 2,4,6-trideoxy-4-amino sugar—d-vicenisamine—were performed.     

A mechanistic study on oxidation of benzylic alcohols with PPh4HSO5 catalysed by manganese(III) porphyrins in homogeneous solution

The oxidation of variously ring-substituted 1-phenylethanols with Ph₄PHSO₅ catalysed by Mn(TMP)Cl and Mn(TDCPP)Cl in the presence of 4-tert-butylpyridine was studied in 1,2-dichloroethane homogeneous solution. The process leads only to C–H bond cleavage products, namely acetophenones. The oxidation rates are independent of the substrate concentration and, when Mn(TMP)Cl is the catalyst, even of the substrate nature. By increasing the concentration of 4-tert-butylpyridine, which acts as an axial ligand of the catalyst, a bell-shaped curve for the rate constants trend is observed. Hammett plots obtained by changing the substituents on the phenyl ring of the benzylic alcohol give different ρ values depending on the technique employed for rate constants determination, i.e., individual or competitive experiment. The observations reported above, together with a KIE of 2.5 in 1- -1-phenylethanol oxidation measured by competitive experiment, are rationalised on the basis of a mechanistic scheme in which the oxo-manganese derivative is formed in the rate determining step of the catalytic process. Furthermore, it is suggested that alcohol dehydrogenation proceeds through a hydride abstraction involving an alcohol-oxo-porphyrinato complex.     

A novel method for the synthesis of chiral epoxides from styrene derivatives using chiral acids in presence of Pseudomonas lipase G6 [PSL G6] and hydrogen peroxide

Chiral epoxidation of styrene and its derivatives was carried out using series of chiral acids and urea hydrogen peroxide (UHP) or aqueous hydrogen peroxide (50%) in two phases under the catalytic influence of immobilized Pseudomonas lipase G6 [PSL G6] at 25-55 °C. A moderate to good yield and enantioselectivities of chiral epoxides were obtained.     

A new polymer-supported Evans-type chiral auxiliary derived from α-hydroxy-β-amino acid, phenylnorstatine: synthesis and application in solid-phase asymmetric alkylation reactions

Based on a new anchoring strategy, a polymer-supported chiral oxazolidinone was prepared starting from (2R,3S)-3-amino-2-hydroxy-4-phenylbutanoic acid (phenylnorstatine, Pns) and Wang resin. Solid-phase asymmetric alkylation on this resin proceeded in high diastereoselectivity comparable to that of conventional solution-phase model experiments. This study suggests that anchoring through the 5-position of oxazolidinone is highly suited to achieving diastereoselective alkylation reactions on solid-support.     

The formal synthesis of lucentamycin A: Construction of cis-2,3-disubstituted pyrrolidine core by application of SmI2-DMPU system

The formal synthesis of lucentamycin A (1) was accomplished in 14 steps from d-serine methyl ester as a starting material. All the requisite stereogenic centers on the pyrrolidine core of 1 were controlled by SmI₂-mediated cyclization. Construction of the methyl unit at the C9 position of 1 was achieved by decarbonylation of lactol 11 with stoichiometric amount of Rh(PPh₃)₃Cl.     

Preparation of compounds in the new dipyrrolo[3,4-b:3′,4′-e]-pyridine series from 1-benzylidene-2,3-dioxopyrrolidines. A variation of the hantzsch synthesis

Treatment of easily prepared l-substituted-4-benzylidene-2,3-dioxopyrrolidines with ammonium formate produces 1,2,4,6,7,8-hexahydro-2,6-disubstituted-8-aryldipyrrolo [3,4-b:3′,4′-e]pyridine-3,5-diones (II), usually in yields of 50 to 60%. Aromatization of the dihydropyridine ring of the hexahydroderivatives II yields corresponding 1,2,6,7-tetrahydro-2,6-disubstituted-8-aryldipyrrolo[3,4-b:3′,4′-e]pyridine-3,5-diones (III). These compounds appear to be the first to incorporate the dipyrrolo[3,4-b:3′,4′-e]pyridine ring system.     

syn-Benzene dioxides: chemoenzymatic synthesis from 2,3-cis-dihydrodiol derivatives of monosubstituted benzenes and their application in the synthesis of regioisomeric 1,2- and 3,4-cis-dihydrodiols and 1,4-dioxocins

cis-2,3-Dihydrodiol metabolites of monosubstituted halobenzenes and toluene have been used as synthetic precursors of the corresponding 3,4-cis-dihydrodiols. Enantiopure syn-benzene dioxide intermediates were reduced to the 3,4-cis-dihydrodiols and thermally racemised via the corresponding 1,4-dioxocins. The syn-benzene dioxide-1,4-dioxocin valence tautomeric equilibrium ratio was found to be dependent on the substituent position. The methodology has also been applied to the synthesis of both enantiomers of the 1,2-(ipso)- and 3,4-cis-dihydrodiols of toluene. This chemoenzymatic approach thus makes available, for the first time, all three possible cis-dihydrodiol regioisomers of a monosubstituted benzene.