Total syntheses of (R)-argentilactone and (R)-goniothalamin via catalytic enantioselective allylation of aldehydes

The total syntheses of (R)-argentilactone (five steps, 25% overall yield) and (R)-goniothalamin (three steps, 61% overall yield) have been described through the enantioselective catalytic allylation of aldehydes (including a propargylic aldehyde) which provided a rapid access to these natural products that display very interesting biological activities.     

Synthetic studies on statins. Part 1: a short and cyanide-free synthesis of atorvastatin calcium via an enantioselective aldol strategy

A short and cyanide-free enantioselective synthesis of atorvastatin calcium has been achieved starting from a commercially available highly substituted 1,4-diketone in an overall yield of 40%. The key step in this approach is the asymmetric aldol reaction of an aldehyde with diketene in the presence of Ti(O-i-Pr)₄–Schiff base complex to create the (5R)-stereochemistry of atorvastatin calcium.     

Rapid access to homoallylic alcohols via Pd(OAc)2 catalyzed Barbier type allylation in presence of DMAP

DMAP was found to accelerate significantly the rate of Pd(OAc)₂ catalyzed Barbier type allylation of carbonyl compounds by allylbromide using SnCl₂·2H₂O as reducing agent. Both aldehyde as well as ketones produced excellent yields within a short reaction time in the presence of 3 mol % of Pd(OAc)₂ and 12 mol % of DMAP at room temperature. Aldehydes could be allylated within 5–10 min whereas, in case of ketones, the reaction completes in 45–120 min.     

Stereoselective VO(acac)(2) Catalyzed Epoxidation of Acyclic Homoallylic Diols. Complementary Preparation of C2-syn-3,4-Epoxy Alcohols

A substrate-controlled stereoselective epoxidation of free and monoprotected homoallylic diols was developed. This second-generation approach is based on the incorporation of a primary hydroxy directing group at the C2 methyl carbon, which changes the nature of the vanadium ester intermediate providing a new diastereoselectivity manifold for the preparation of 3,4-epoxy alcohols. This modification favored the formation of the challenging C2-syn epoxy alcohol product not previously available using the standard homoallylic alcohol substrates. These new epoxy alcohol diastereomers expand the scope and generality for the utilization of 3,4-epoxy alcohols as precursors for stereoselective polypropionate synthesis.     

Pd(OAc)2-catalyzed C-H activation of indoles: a facile synthesis of 3-cyanoindoles

Indoles undergo smooth cyanation with CuCN in the presence of 20 mol % Pd(OAc)₂ and 40 mol % CuBr₂ in DMF to produce a wide range of the corresponding 3-cyanoindoles in good yields with high regioselectivity.     

Oxidative thermolysis of Mn(acac)3 on the surface of γ-alumina support

Precipitated γ-alumina support was decorated with Mn(acac)₃ by incipient wetness impregnation with toluene solutions containing Mn(acac)₃ in amount equivalent to loading of 0.35, 0.74, 1.38, 2.38 and 3.50 Mn(acac)₃ moleculs per nm² of the support. In order to evaluate the mechanism of Mn(acac)₃ interaction with the surface of γ-alumina support and subsequent transformations of the supported Mn(acac)₃ species, oxidative thermolysis of Mn(acac)₃/Al₂O₃ samples in air was studied by diffuse reflectance FTIR, thermogravimetric analysis (TG/DTG), differential thermal analysis (DTA) and XRD. It has been found out that decoration of γ-Al₂O₃ support with Mn(acac)₃ results in the formation of surface bound Mn(acac)_3−x species when Mn(acac)₃ loading does not exceed 1.38 Mn(acac)₃/nm². At higher Mn(acac)₃ loading the formation of the supported bulk-like Mn(acac)₃ species also occurs. The interaction of Mn(acac)₃ molecules with the support surface occurs via substitution of acetylacetonate ligand(s) with the oxygen atom of surface hydroxyl group(s) accompanied by elimination of acetylacetone molecules. The evolved acetylacetone reacts with the alumina surface that results in the formation of surface Al(acac)_3−x species. The oxidative thermolysis of Mn(acac)_3−x species on the surface of γ-alumina proceeds via partial elimination of acetylacetonate ligands and partial oxidation of the remaining ligands without destruction of their cyclic structure within 425-550 K. The complete oxidative destruction of acetylacetonate ligands takes place within 600-700 K and results in the formation of manganese oxide species on the alumina surface. The dispersed surface manganese oxide species originate upon the oxidative thermolysis of the surface bound Mn(acac)_3−x species while crystalline Mn₂O₃ phase results from the supported bulk-like Mn(acac)₃ species.     

Michael reaction of indoles with 3-(2′-nitrovinyl)indole under solvent-free conditions and in solution. An efficient synthesis of 2,2-bis(indolyl)nitroethanes and studies on their reduction

Michael reaction of 3-(2′-nitrovinyl)indole with eight 3-unsubstituted indoles on TLC-grade silica gel furnished unsymmetrical bis(indolyl)nitroethanes in 7-12 min under microwave irradiation and in 8-14 h at rt. In contrast, the p-TsOH-catalysed reaction of the nitrovinylindole with the 3-unsubstituted and two 3-substituted indoles in solution under reflux furnished both unsymmetrical and symmetrical bis(indolyl)nitroethanes, the latter resulting from novel tandem Michael addition-elimination-Michael addition reactions. The synthesis of a 2′,3″-bis(indolyl)nitroethane, the precursor core structure of two bioactive marine metabolites, and the reduction of 2,2-bis(3′-indolyl)nitroethane to the corresponding ethylamine, isolated as its N-acetyl derivative, have been achieved. Significantly, attempted hydrolysis of three nitronates, derived from the corresponding bis(indolyl)nitroethanes, with buffered aqueous TiCl₃ has led to the first isolation of oximes (syn/anti-mixture) as the only products.     

A simple and efficient synthesis of gem-dihydroperoxides from ketones using aqueous hydrogen peroxide and catalytic ceric ammonium nitrate

Ketones were efficiently converted into the corresponding gem-dihydroperoxides in high yields within a short period of time on treatment with aqueous H₂O₂ (50%) in the presence of a catalytic amount of CAN in acetonitrile at room temperature.     

A facile synthesis of naturally occurring 5-(3-indolyl)oxazoles

A simple and efficient synthesis of naturally occurring 5-(3-indolyl)oxazoles is described. The key steps of this convergent approach are the formation of a 3-tosyloxyacetyl-1-benzenesulfonylindole, a 3-amino-acetyl-1-benzenesulfonylindole hydrochloride and cyclodehydration of an α-acylaminoketone.     

Nickel-catalyzed organozinc-induced unexpected 1,3-migration of tert-butyl from sulfur to carbon in N-tert-butanesulfinyl iminoacetates

The nickel-catalyzed reaction for an unexpected 1,3-migration of tert-butyl from sulfur to carbon, upon treatment of functionalized N-tert-butanesulfinyl iminoacetate in the presence of organozinc reagent, was developed. The generality has been explored by considering the flexibility in the structure of each reactive component, organozinc halide and N-tert-butanesulfinyl iminoacetate.     

A facile protocol for the synthesis of mono-N-methyl anilines via formimidate intermediates

A general procedure for the preparation of mono-N-methyl anilines has been developed with excellent yields. This protocol relies on a NaBH₃(OAc) reduction of formimidate intermediates that are quantitatively generated by treatment of primary substituted anilines with triethyl orthoformate under the catalysis of MCM-41-SO₃H mesoporous zeolite. The newly developed procedure was facile, efficient, and environmentally benign.     

A facile large scale synthesis of optically active 3-amino-5-(2-pyridyl)-1,4-benzodiazepin-2-one derivatives

A facile method for the synthesis of 3-amino-5-(2-pyridyl)-1,4-benzodiazepin-2-ones (8) mediated by benzotriazole is described. The synthesis and optical resolution of the product by fractional crystallisation proceeds in high yield, under mild conditions and without recourse to toxic reagents or chromatographic separations and hence is amenable to the large scale preparation of these important precursors to potent CCK receptor ligands.     

A facile intramolecular azido/amido reductive cyclization approach: synthesis of pyrrolobenzodiazepines and their dimers

A new synthetic pathway has been developed for the preparation of imine-containing pyrrolo[2,1-c][1,4]benzodiazepines (PBDs) and their dimers. Selective reduction of aromatic azides as well as aliphatic amides in a single step leading to an intramolecular reductive cyclization process by employing LiAlH₄ or LiBH₄ provides the cyclized imines.     

A facile synthesis of 2-(N-alkylamino)-pyrimidin-4-one derivatives

Substituted 2-(N-alkylamino)-pyrimidin-4-ones were synthesized from N-alkyl β-amino acid esters starting with guanidinylation using Pbf-activated thiourea. The six-membered pyrimidinones were obtained in good yields via intramolecular cyclization during TFA cleavage of the Pbf protecting group.     

Synthetic studies on basidifferquinones: the first synthesis of (±)-basidifferquinone C

Basidifferquinones, isolated from Streptomyces sp., are potent inducers for fruiting-body formation of a basidiomycete Polyporus arcularius. Construction of the basic framework of basidifferquinones and the first synthesis of (±)-basidifferquinone C were accomplished by starting from 3,5-dihydroxy-2-naphthoic acid.     

SnCl2·2H2O-mediated Barbier-type allylation: A comparative evaluation of the catalytic performance of CuI and Pd(OAc)2

A systematic investigation has been carried out for the allylation of carbonyl compounds under SnCl₂·2H₂O-mediated Barbier-type conditions, using CuI and Pd(OAc)₂ as catalysts. Ketones, which are not reactive under the influence of CuI, however, could be activated by using Pd(OAc)₂ as a catalyst.     

Novel solid-supported dimerization-heteroannulation of chalcones: simple and efficient synthesis of 2,4,6-triaryl-3-methylarylpyridines

2,4,6-Triaryl-3-methylarylpyridines were obtained, in 60-70% yield, by a novel one-pot solventless solid-supported dimerization-heteroannulation reaction of chalcones and compounds possessing terminal -CONH₂ functionality, at 125-135 °C, using immobilized Bi(III) nitrate and Zn(II) chloride as co-catalyst. Initially, chalcones were prepared, in nearly quantitative yield, by a modified aldol condensation, in neutral aqueous medium, in the presence of p-toluenesodium sulfonate.     

Mild and practical stereoselective synthesis of (Z)- and (E)-allyl bromides from Baylis-Hillman adducts using Appel agents (PPh3/CBr4): a facile synthesis of semiplenamides C and E

Appel agents (PPh₃/CBr₄) have been utilized for high-yielding stereoselective synthesis of (Z)- and (E)-allyl bromides from Baylis-Hillman adducts at room temperature. The method has been applied for the synthesis of naturally occurring bioactive fatty acid amides, semiplenamides C and E.     

Synthetic studies of carzinophilin. Part 3: Synthetic approach toward carzinophilin and successful synthesis of 13-O-desacetyl-12,13-di-O-benzyl-4-O-methylcarzinophilin

The synthetic procedures of the title compound (2), a protected form of carzinophilin (1), were developed. While efforts toward the total synthesis of 1 failed, comparison of the ¹H NMR spectra of 2 and some other related compounds with that of 1 provided definite support for the absolute stereochemistry of 1 which has a complicated history regarding its structure.     

A simple and facile stereoselective synthesis of (Z)- and (E)-allyl halides catalyzed by silica supported sodium hydrogen sulfate: factors influencing the yields and stereochemistry of allyl halides

A simple, mild and efficient stereoselective synthesis of (Z)- and (E)-allyl bromides and iodides has been developed by treatment of the Baylis-Hillman adducts with lithium bromide and iodide, respectively, in methylene chloride catalyzed by silica supported sodium hydrogen sulfate at room temperature. The role of various solvents, different reacting metallic halides, nature of the adducts and activity of several heterogeneous catalysts on the yields and stereochemistry of the products have been thoroughly studied.