Current Organic Synthesis - Volume 11, Issue 2, 2014

This review covers the functionalization of 4,7-dihydroindole derivatives as synthetic equivalents (synthons) for 2-substituted indoles.

Iminosugars continue receiving a great deal of attention from chemists and biochemists for their potential as pharmaceutics. This is a comprehensive review of the methods found in the literature for the synthesis of piperidine, pyrrolidine, indolizidine, and pirrolizidine iminosugars, starting from D/L-erythrose and D/L-threose carbon chains (tetroses). This review shows the crescent popularity of small molecules to build up iminosugar molecules. Methodologies described herein utilize inexpensive commercial materials. The synthesis of the four tetroses is included referring old and modern methodologies.

Enantioselective epoxidation of olefins is a useful synthetic route in organic synthesis, as a wide variety of olefins is available and optically active epoxides can be converted into various functionalities with high regio- and stereoselectivity. Chiral manganese(III)- salen catalyst, which is commonly known as the Jacobson-Katsuki catalyst, has been reported as selective and efficient catalyst for the epoxidation of unfunctionalised alkenes in homogeneous phase, using a wide range of oxidants-iodosylbenzene, sodium hypochlorite, mchloroperoxybenzoic acid, hydrogen peroxide, etc. However, this homogeneous catalyst cannot be separated from the reaction media and, subsequently, cannot be recycled. Moreover, it suffers deactivation in homogeneous phase by formation of dimeric μ-oxo-manganese(IV) species, which are inactive in the alkene epoxidation. One way of improving the chemical process, preventing the requirement for a laborious and inefficient extraction processes, is to immobilize the homogeneous catalyst on a solid support. Numerous accounts for salen immobilization using diverse kinds of inorganic materials, organic materials and inorganic-organic hybrid materials have been firstly outlined in this review.

γ-Hydroxybutenolides are readily available reagents that are useful starting materials for the synthesis of simple and complex compounds. This review will discuss the role tautomerism plays in the reactivity profile of γ-hydroxybutenolides, the major modes of reactivity of γ-hydroxybutenolides, and the application of this methodology for the synthesis of biologically important molecules.

Marine natural products are recognized as a fruitful source of drug development due to their rare structural entities and diverse biological activities, and consequently, publicized number of metabolites as new medicines. Although extensive progress has been made in identifying novel bioactive molecules from marine source, endeavors to explore these molecules for medicinal applications are much needed. Marine fungi are one of the important sources of natural products, exhibiting a wide range of biological activities. (+)-Varitriol, isolated from the marine fungus Emericella variecolor, has shown 100-fold increased potency over the mean toxicity towards variety of cancer cell lines. Hence (+)-varitriol, an antitumour marine natural product has been a fascinating target for total synthesis over the last decade. The intense search for developing new approaches coupled with its biological activity has resulted in a wealth of methods towards the syntheses of this molecule. But, unfortunately only limited analogues have been synthesized and evaluated for their biological activities. Thus, there are still demands to modify aromatic part as well as sugar moiety of varitriol, which could provide the opportunity for further SAR studies to discover potential lead anticancer agents. This review describes the different strategies developed for the syntheses of varitriol and its analogues in various laboratories around the world covering literature from 2002 till date. The construction of the challenging and fashionable furanoside ring as well as substituted styrene derivatives are crucial steps in most of the reported synthetic endeavors.

Hydrophilization of Polyamide 46 (PA46) via modification with acetaldehyde in continuous phase was studied. The chemical modification of PA 46 with acetaldehyde resulted in a water-swollen polymer with hydrophilic property. The polyamide 46 undergoes a nucleophilic addition with acetaldehyde in the presence of aluminum chloride as a catalyst. The extent of bulk hydroxyethylation using AlCl3 resulted in 95.65% modification counted as total N-hydroxyethylated polyamide 46. The modification resulted in improved hydrophilic properties, and a maximum surface free energy of 44.6 mJ/m2 was achieved after 3 h reaction, whereas the unmodified PA46 had a surface free energy of 11.2 mJ/m2. In addition, thermal properties of the polymers were studied using differential scanning calorimetry and thermogravimetric analyses. The functionalization leads to decrease in the crystallization energy from 88 J/g to 51 J/g, while the melting energy is changed from 110 J/g to 53 J/g. Furthermore, the thermal stability of the PA46 to pyrolysis was diminished after hydroxylation.

A series of sulfides was successfully synthesized by a thiol-disulfide exchange reaction using disulfides as the reactive substance. After cleavage of S-S bonds by ammonium thioglycolate catalysis, Michael addition reactions were performed using various acceptors in one-pot. The catalyzed-reaction mechanism has been discussed based on the by-products. In addition, 2,3H-1,5- benzothiazepines were also successfully synthesized from 2,3H-1,5-benzothiazepine-4(5H)-one with satisfactory yields using Lawesson’s reagent.

BINOL-based diphosphite ligands containing oxygen or nitrogen heteroatoms are currently a new class of promising ligands for homogeneous catalysis. Herein we present a useful strategy to synthesize ditopic (R)-BINOL-based diphosphites, containing pyridyl or propyl ether bridges between BINOL fragments in high isolated yields (50-92 %). Their rhodium complexes were evaluated in styrene hydroformylation, in which a moderate regioselectivity for the branched aldehyde was observed. The addition of a lithium salt led to a significant increase in the regioselectivity (25 %) for the branched aldehyde. This interesting observation has been rationalized based on a full two-level factorial design with 3 factors, including pressure, temperature and the Li/Rh ratio, using Rh/10 as model catalyst. The improvement of the regioselectivity in the presence of lithium salts has been interpreted through 31PNMR spectroscopy and semiempirical PM6 computational studies.

Pyrrolidine was used as a catalyst for the simple, convenient, and highly efficient synthesis of dihydropyrano[2,3-c]pyrazole derivatives. Four-component one-pot reactions of β-ketoester, hydrazine, ethyl glyoxalate or ethyl pyruvate, and malononitrile in ethanol under reflux conditions led to excellent yields of 79%-94%.