Advances in Organic Synthesis

Phosphorus- and nitrogen-containing ligands are among the most important and widely used heterodentate ligands for transition-metal homogeneous catalysis (asymmetric or otherwise). The present review combines information on recent advances in the syntheses of these ligands, their coordination chemistry with transitionmetals and their applications to homogeneous catalysis.

Transition metal-catalyzed [2+2] cycloadditions between bicyclic alkenes and alkynes provides an efficient method for the construction of cyclobutene rings. Various transition metal complexes, including those of cobalt, nickel, ruthenium, rhodium, and rhenium, have been used to catalyze [2+2] cycloadditions between bicyclic alkenes and alkynes. The purpose of this review is to summarize and discuss the various aspects of transition metal-catalyzed [2+2] cycloaddition between bicyclic alkenes and alkynes, including the development of metal catalysts, the mechanisms of the cycloadditions catalyzed by different metal catalysts, the reactivity of the alkene and the alkyne components in the cycloaddition, the compatibility of different functional groups on the alkene and the alkyne components, the chemo- and regioselectivity of the cycloadditions between unsymmetrical substrates, and the asymmetric induction studies using chiral auxilliaries on the alkyne component in addition to the use of using chiral ligands. The scope and limitations of each catalyst in the [2+2] cycloadditions will also be discussed.

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. Part 1 describes the preparation of polyamino, poly(amino-amido), polyamido macrocycles by procedures involving mainly nucleophilic substitution and acylation reactions, but also ring closing metathesis, multicomponent and click reactions in the cyclization step.

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 methods, among which the reaction of primary amines with carbonyl compounds to form polyimino macrocycles. The rigidity and restricted flexibility of the reaction partners is generally required to get success in cyclization. Alternatively, cyclization can be favored by using a metal template. The carbon stereocenters in the formed macrocycle are usually present in the starting nitrogen-containing reagent, e.g. amine, diamine, α-aminoacid and their derivatives. Preformed imines can be also used as precursor of macrocyclic rings. Intrinsically chiral porphyrins, lacking carbon stereocenters, and bridged bis(macrocyclic) compounds incorporating porphyrins (strapped porphyrins) and analogous macrocycles have been also surveyed. 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.

In this part other procedures of glycosylation reactions by direct activation are presented. We will focus on the n-pentenyl glycoside, the O-alkylation and the trichloroacetimidate methods. The use of glycosyl phosphates and glycals in glycosidation reactions are also discussed. Updated examples of these glycosylation methodologies involving total synthesis of oligosaccharides and related compounds are considered.

As a consequence of the renewed interest of β–lactams in organic and medicinal chemistry, research in this field is constantly providing new appealing advances. This chapter focuses on synthetic aspects related to the generation of this four-membered heterocyclic ring, published since 2000, with special emphasis on stereoselective synthetic approaches. The compendium deals with methods for achieving diastereo- and enantioselectivity during [2+2] cycloadditions, with the Staudinger reaction still as first choice, but also important achievements have been published for the imine-enolate condensation, the carbonylative cycloaddition and the Kinugasa reaction. Significant success has also been accomplished in the synthesis of innovative 2-azetidinones through the formation of a single bond. In this respect, the C3-C4 bond formation, through intramolecular cyclization of linear epoxy or halo derivatives and the carbenoid C-H insertion are among the most effectively exploited procedures. In addition, adaptation of most procedures to solid-phase methodologies has facilitated the generation of molecular diversity based on the β–lactam skeleton.

This article describes the progress made in the synthesis of five- and six-membered heterocyclic rings by the application of the ring-closing metathesis reactions during the period of 2007-2012.

Synthetic amino acids have particular appeal to extend our understanding of protein structure and stabilization into the realm of folded, non biological polymers. Chemists are now beginning to design biomimetic amino acids that can form both secondary and tertiary structures. An overview of the synthesis of non-protein amino acids recently used in the design of conformationally well-defined foldamers—artificial oligomers that also adopt well-defined folded conformations— are discussed.