Current Organic Synthesis - Volume 6, Issue 2, 2009

Chiral non-racemic perazamacrocyles containing three or more nitrogen atoms in the form of different functions (amine, amide, imine) are prepared from optically active amines, diamines, α-aminoacids, and their derivatives, by properly selected methodologies. The many applications of these optically pure perazamacrocycles rely on the basic and/or hydrogen bond donor properties of the nitrogen functions and include metal ions coordination, supramolecular chemistry, material science, molecular and enantioselective recognition, and asymmetric catalysis.

The formation of chiral non-racemic perazamacrocyles containing three or more nitrogen atoms in the form of identical of different functionalities can be achieved by diverse methodologies which usually exploit the sequential formation of carbon-nitrogen bonds by reaction of nucleophilic nitrogen functions with electrophilic compounds. The rigidity and restricted flexibility of the reaction partners is generally a requisite for the successful cyclization, which can be alternatively accomplished by the use of a metal template. The carbon stereocenters in the formed macrocycle are generally present in the starting nitrogen-containing reagent, e.g. amine, diamine, α- aminoacid and their derivatives. Intrinsically chiral porphyrins, lacking carbon stereocenters, have been also prepared. Chiral perazamacrocycles and their metal complexes have found applications in the fields of biomedical research, diagnosis, anion sensing, molecular recognition, enantiomeric discrimination, asymmetric catalysis, and material chemistry.

The ubiquity of piperazine-2,5-dione core (2,5-diketopiperazine, DKP) in biologically active natural products and the preponderance of its heterocyclic framework in many drugs, has encouraged the development of methods for the selective functionalisation of readily available piperazine-2,5-dione precursors. C-functionalisation using DKPs as electrophilic glycine templates is generally mediated by N-acyliminium ions. These intermediates show highly versatile reaction characteristics, which are reflected in an impressive number of synthetic applications. However, even in some very comprehensive reviews dealing with N-acyliminium ions, references to these species derived from piperazine-2,5-diones are scarce. This review is devoted to fill this gap, placing emphasis upon the most suitable precursors of endocyclic and exocyclic acyliminium ions derived from piperazine-diones and their synthetic applications. Other more complex structures that include this framework or a related portion, such as pyrazino[1,2-b]isoquinoline-1,4-diones or the pyrazino[2,1-b]quinazoline-3,6-dione system, are also overviewed.

In recent years the development of transition metal complexes having in its structure pincer type ligands has received considerable attention. Nowadays these complexes are designed and synthesized not just for the mere structural interest but for the great number of potential applications these compounds may have. Thus, the present paper presents and discusses recent advances (covering until early 2008) on the chemistry of aromatic based PCP and PNP pincer transition metal complexes, highlighting recent advances on their preparation and use as homogeneous catalysts in cross-coupling reactions and other industrially relevant organic transformations.

The Pschorr reaction is a classical ring closure process for the formation of polycyclic systems in which two aryl moieties are joined together. It represents a bridge that connects diazonium ion chemistry with PAH synthesis. The Pschorr reaction has been employed as a key step in a number of carbocyclic and heterocyclic ring forming transformations for the synthesis of complex polycyclic molecules. Our continuing interest in diazonium ion chemistry and PAH chemistry prompted us to review the status of this transformation and to summarize the more recent developments in the use of this classical reaction.

The use of fluoride ion as a base and nucleophile has been widely exploited in organic synthesis. On the other hand over the last few decades the fast-growing development of polymer supported reagents has led to the synthesis of a variety of fluorides on solid support. Such compounds display some major benefits: i.e they are less hygroscopic, easy to recover and to recycle. Tetraalkylammonium fluorides represent some of the most common available sources of fluoride, their solid-supported analogues have been employed in a large range of organic reactions.