Current Organic Synthesis - Volume 10, Issue 3, 2013

The synthetic potential of the photo-oxygenation has been discussed. It provides an exquisite regioselective, and in many cases stereoselective, entry into synthetically useful feedstock using an environmentally benign oxidant. Allyl hydroperoxides are the principal products when unsaturated compounds undergo photo-oxidation. The singlet oxygen ene reaction is bimolecular process with a rate that depends on concentration of both the substrate and singlet oxygen. Convenient rates are achievable in many common organic solvents using photosensitization. However, condensed phase photo-oxidation conditions suffer from several drawbacks. Therefore, the area of polymer-supported catalysis has been extensively studied. The singlet oxygen ene reaction of allylic stannanes leads to formation of Mene, H-ene and cycloaddition products. Its relative yields depend on structural and environmental conditions. The considerable efforts have been made to optimize the selection of the ideal solvent to carry the photo-oxidation. It has been observed that in the presence of different salts such as LiClO4 reaction rates are considerably faster. Noticed effects depend on the concentration of the salt and vary with change of the solvent. Results of photo-oxidation of phenols indicate that yield of the reaction and type of products dependz on pH of studied solution and the addition of LiClO4, CF3SO3Li or Bu4NF which catalyze this reaction. The catalytic effect of LiClO4 on reactions of singlet oxygen with different olefins and allyltin compounds has been explained as a result of stabilization of the transition state by the ionic medium. It also occurs that physicochemical properties of organic solvents and effects joined with solvation by them LiClO4 are responsible for this catalysis.

Several compounds that contain the 2-aminothiophene structural motif have been found to be promising pharmacological agents, such as the antipsychotic drug olanzapine, which has already been commercialised. There are many approaches to the synthesis of 2-aminothiophenes; however, the Gewald reaction is considered to be the simplest and most convergent method for generating these heterocycles. The reaction is reviewed from its original development to the most recent advances in terms of substrate scope, reactivity, reaction conditions, and synthetic applications.

Glycosylphosphatidylinositol (GPI) anchorage of proteins and glycoproteins onto the cell surface is ubiquitous in eukaryotes, and GPI-anchored proteins and glycoproteins play an important role in many biological processes. To study GPI anchorage and explore the functions of GPIs and GPI-anchored proteins and glycoproteins, it is essential to have access to these molecules in homogeneous and structurally defined forms. This review is focused on the progress that our laboratory has made towards the chemical and chemoenzymatic synthesis of structurally defined GPI anchors and GPI-anchored peptides, glycopeptides, and proteins. Briefly, highly convergent strategies were developed for GPI synthesis and were employed to successfully synthesize a number of GPIs, including those carrying unsaturated lipids and other useful functionalities such as the azido and alkynyl groups. The latter enabled further site-specific modification of GPIs by click chemistry. GPI-linked peptides, glycopeptides, and proteins were prepared by regioselective chemical coupling of properly protected GPIs and peptides/glycopeptides or through site-specific ligation of synthetic GPIs and peptides/ glycopeptides/proteins under the influence of sortase A. The investigation of interactions between GPI anchors and pore-forming bacterial toxins by means of synthetic GPI anchors and GPI analogs is also discussed.

This review covers the recent advances concerning the elusive enantioselective biomimetic cyclization of functionalized unsaturated compounds promoted by halonium ions. The asymmetric halocyclization of multiple carbon-carbon bonds is an important class of organic reactions as it provides stereodefined carbon-halogen bond-containing compounds, which are ubiquitous in nature and other bioactive molecules. Although the halocyclization reaction is known since long, attempts to carry out this electrophilic cyclization process in an asymmetric way had largely been unsuccessful and the first synthetically useful examples have appeared in the last few years. The most important progresses in this field are summarized.

A variety of chiral bisamide ligands have been prepared and widely used in asymmetric catalytic syntheses with highly regioand enantioselective products, especially in the transition-metal-catalyzed asymmetric allylic alkylation reactions. The achievements in the asymmetric allylic alkylation reactions with various nucleophiles have been reviewed. The applications of some typical chiral bisamides in decarboxylative asymmetric allylic alkylation of enol carbonates, [3+2] cycloaddition of vinyl cyclopropanes and alkylidene azlactones, and aldol reactions are also introduced.

The synthesis of α,β-dehydro-α-aminophosphonic and α,β-dehydro-α-aminophosphinic acid derivatives is discussed. The most important synthetic pathways to the above-mentioned compounds have been divided into four groups depending on the type of bond formed as the last one. The configuration at the C=C double bond can be established based on the specific coupling constants 3JHP and 3JCP for the appropriate Z- and E-stereoisomers. The application of α,β-dehydro-α-aminophosphonates and α,β-dehydro-α- aminophosphinates, particularly in the enantioselective catalytic hydrogenation, is also discussed.

Development of efficient routes to many kinds of fused heterocycles is an attractive area of research since these compounds constitute one of the most interesting divisions of organic chemistry. A majority of the compounds produced by nature as well as significant numbers of compounds synthesized in the industrial sector each year have heterocyclic rings as part of their structures. This review survey research works on the specific synthesis of furo-, pyrrolo-, and thieno-fused heterocycles by multi-component reactions over the last ten years. Different approaches for the synthesis of such systems are discussed.

A highly enantioselectiveorganocatalyticnitromethylphenylsulfone addition to aliphatic α,β-unsaturated aldehydes is reported. The reaction is catalyzed by simple and commercially available secondary amines, affording the cyclic compounds in moderate yields, good diastereoselectivities and excellent enantioselectivities.

The different base-promoted regioselective reactions between dialkyl (2E,3E)-2-[(dimethylamino)methylene]-3-(1-methyl-2,5- dioxoimidazolidin-4-ylidene)succinates and 1,2-diaza-1,3-dienes are investigated. Under the appropriate reaction conditions it is possible to turn the synthesis towards 1,3-dioxo-2,3,7,7a-tetrahydro-1H-pyrrolo[1,2-c]imidazoles or 1,3-dioxo-1,2,3,5-tetrahydroimidazo[1,5- a]pyridines. Both these transformations proceed via a double-Michael-addition.

The C-C coupling of bicyclic alkene 4 with aryl and heteroaryl iodides gave under reductive Heck conditions the Caryl( hetaryl), N-[((4-pyrimidin-2-yl)piperazin-1-yl)butyl]substituted bicyclic imides 5a-f. The [3+2] cycloadditions of 4 with various nitrile oxides yielded the bridged isoxazoline derivatives 6-8 with potential biological activity.

The cyclocondensation of alkynyl ketones with 1,3-dicarbonyl compounds in the presence of NaOH in DMF at 80 °C affording polysubstituted phenols with high atom-efficiency in moderate to good total yields is developed.

A simple, convenient and highly efficient aerobic oxidative trimerization of indoles has been developed using TEMPO in air, and the corresponding 3-(1H-indol-3-yl)-3,3'-biindolin-2- one derivatives were obtained in moderate to excellent yields. This methodology provides an alternative approach for the direct generation of all-carbon quaternary centers at the C3 position of indoles.